ACE I/D) polymorphism and the α-actinin-3 gene (ACTN3) R577X polymorphism have been most widely studied for such association analysis. However, the findings are frequently heterogeneous. We aim to summarize the associations of ACE I/D and ACTN3 R577X with sport performance by means of meta-analysis.Genetic polymorphism is suggested to be associated with human physical performance. The angiotensin I-converting enzyme insertion/deletion  with increased possibility of physical performance . With respect to sport discipline, the II genotype was found to be associated with performance in endurance athletes . On the other hand, no significant association was observed for ACTN3 RR genotype as compared to X allele carriage (XX+RX) . However, when restricted the analyses to power events, a significant association was observed .A total of 366 articles on ACE II genotype and endurance events and between ACTN3 R allele and power events. The findings suggest that the genetic profiles might influence human physical performance.Our results provide more solid evidence for the associations between  Elite athletes are defined as the one who has competed at a national or international level in a given sport ACE gene ACE insertion/deletion  polymorphism has been related with improvements in performance and exercise duration in a variety of populations. The I allele, which represents an insertion of 287 bp, is associated with lower serum ACTN3 has also been well studied as a target gene. The ACTN3 gene encodes the protein α -actinin-3, which is almost exclusively expressed to sarcomere of the fast glycolytic type II fibers that are responsible for the generation of rapid forceful contractions during activities such as sprinting and weightlifting ACTN3 gene that results in the replacement of an arginine (R) with a stop codon (X) at amino acid 577  can create two different versions of the ACTN3 gene. Both of these two versions are common in the general population. However, the findings on the relations between genetic polymorphisms and sports performance are frequently heterogeneous.Here, we specifically consider two genes which have been extensively studied for the association with athletic ability, namely, the angiotensin I-converting enzyme (ACE) and α-actinin-3 (ACTN3). The first evidence of genetic polymorphisms influencing human physical performance is reported for ACE and ACTN3 genetic polymorphisms by means of meta-analysis, which might provide more solid evidence as compared with individual reports.In this article, we aim to summarize the associations of sport performance with ACE and 88 articles focused on ACTN3 were achieved by literature search separately, from PubMed and EMBASE, using different combination of key terms. As shown in ACE or ACTN3 were screened separately. After excluding papers whose topics are not relevant, 75 abstracts and 63 abstracts were retrieved for next step. After abstract evaluation, 37 studies addressing the association of ACE polymorphisms and sport performance, and 35 studies addressing the association of ACTN3 polymorphisms and sport performance were identified for detailed full text evaluation. Finally, 25 articles addressing ACE and 23 articles addressing ACTN3 were included in this study, respectively. Among them, there are 6 articles reported data on both ACE and ACTN3. Please refer to Table S1 for more detailed information on study identification.After excluding the overlapped results between the databases, a total of 366 articles about Table S2, not all included articles provided necessary information for sub-group analysis. Among the 25 articles provided information of ACE I/D polymorphism, 10 studies were included in gender sub-group analysis, 17 studies and 13 studies were included in endurance and power groups for sport discipline sub-group analysis, respectively. In the 23 articles provided data of ACTN3 R577X polymorphism, 13 studies were included in gender sub-group analysis, 15 studies and 18 studies were included in endurance and power groups for sport discipline sub-group analysis, respectively.As shown in ACE II genotype compared to D allele carriage (DD+ID) with increased possibility of physical performance . Medium heterogeneity between studies  was observed. No significant publication bias was observed . In the subgroup analysis with respect to gender, no significant relationship was observed for males  and females . In the subgroup analysis with respect to ethnicity, significant relationships were observed for Westerns . But with respect to sport discipline, the II genotype was found to be associated with performance in endurance athletes  but not in power athletes . When the analyses were based on a dominant model  . Heterogeneity between studies was medium . No substantial publication bias was observed . When restricted the analyses to power events, a significant association was observed . In the analyses based on dominant model as shown in ACE I/D and ACTN3 R577X by means of meta-analysis. Significant relations were observed between ACE II genotype and endurance events, and ACTN R allele and power events, respectively. Subgroup analyses suggest gender, ethnicity and sport discipline might explain, at least in part, the existing heterogeneity between included studies.This review estimated the association of human sport performance with ACE I/D polymorphism in intron 16 affects the function of the gene, differentiating the enzymatic activity of angiotensin convertase in the blood ACE polymorphism and sport performance ACE I allele and longer distance sport events ACE D allele and ACE DD genotype in Israeli elite marathon runners seems to be higher than in sprinters, which suggested a positive association between the D allele and the likelihood of being an elite endurance athlete in some ethnic groups ACE I allele and endurance sport events, but it was very close to be so . Moreover, a significant association between ACE II genotype and endurance group was observed . These results may suggest for larger population and more specific studies in different ethnic groups.It has been accepted that a number of elite athletes were natural. Athletes might be inherently predisposed towards specialist performance in one area. A vast array of human phenotypes was suggested to influence sports performance, such as muscle strength, skeletal structure, tendon elasticity, and heart and lung size. These phenotypes themselves are influenced by a variety of other processes and cellular pathways which are eventually influenced by a large number of individual and relevant genes. The ACTN3 gene encodes for the synthesis of a-actinin-3 in skeletal-muscle fibres, a sarcomeric protein necessary for producing ‘explosive’ powerful contractions. A premature stop codon polymorphism in ACTN3 was first described by North and colleagues ACTN3 genotype and athletic performance ACE I/D, researchers generally concentrate on association between ACTN3 R577X and power events. Some articles have consistently reported a strong association between RR genotype and elite power performance ACTN3 R allele was suggested to be associated with power performance, ACTN3 XX might be postulated to contribute to endurance performance theoretically. However, reports from Asians and Africans suggested that ACTN3 deficiency might not associated with endurance performance The ACE I/D polymorphism research published during 1998–2010 which suggests that the I allele is tending to be associated with endurance sports ACTN3 and athletic status up to November 29, 2010 and observed an overrepresentation of the ACTN3 R577X RR genotype in power athletes in Europeans ACTN3 R577X genotype and sport performance.With respect to the rapid increase in the number of original researches in this area, review articles have been published from different perspectives There are some limitations of this systematic review that should be kept in mind. First, the potential confounding effect of performance level was not considered in present study because of the different criterions of elite athletes. Second, because not all necessary information could be obtained from all included studies, more detailed sub-analysis was limited. For example, the crude division of ethnics groups into ‘Asian’, ‘African’ and ‘Western’ may make the analyses be prone to bias. Therefore, further studies from different populations are warranted to verify the current findings. Third, only articles provided data on both athletes and sedentary controls were included in this present study, which might introduce potential selection bias. Fourth, although studies reporting negative genetic association are less likely to be published than others showing ‘statistical significance’ (‘positive results’), no evident publication bias was observed in our present analyses (p>0.05). Finally, due to the variety of definition of endurance/power events and some studies reported data of mixed sport disciplines, phenotypic heterogeneity cannot be excluded.ACE I/D and ACTN3 R577X polymorphisms. The results consistently provided more solid evidence for associations between ACE II genotype and endurance events, and between ACTN R allele and power events. Our findings provided more solid evident to support that human physical performance might be influenced by genetic profiles.In conclusion, the present study summarized the associations of sport performance with ACE/ACTN3 genetic polymorphisms and sports performance were identified by searching for published original articles in PubMed (1946- ) and EMBASE (1974- ) until October 31, 2012. Combinations of the key words “sport” and “ACTN3” or “alpha-actinin-3” were used to screen for potentially relevant studies focused on ACTN3. Combinations of the key words “sport” and “ACE” or “angiotensin-converting enzyme” were used to screen for potentially relevant studies focused on ACE. Additional studies were also identified by cross-referencing Studies addressing relations between ACE or ACTN3 among both athletes and sedentary health controls were considered. If the study was reported in duplicate, the version firstly published was included. Short reports or letters were included if the distribution data of ACE or ACTN3 could be obtained. Exclusion criteria were: (i) review articles, congress abstracts, commentaries or other unoriginal studies; (ii) studies reported in languages other than English; (iii) articles did not provide necessary data; (iv) departure from HWE was detected in a control group.Original articles presented case-control or cohort studies on human and published in English were considered. Articles reported the distribution of single nucleotide polymorphism of Table S3 for the sport classify.For all studies, we extracted the following data from original publications: first author and year of publication; distribution of genotypes for each polymorphism among athletes and controls, characteristics of the study design and the study population  We defined different sport disciplines into two divide category, as endurance and power and please refer to 2 test. Stratified analyses were conducted with respect to gender, sport discipline and host ethnicity. The latter was categorized as Africans, Asians and Westerns (Europeans and Americans). Because of the limited number of publications in Americans, they were sub-grouped to Westerns combined with studies from Europeans. Begg rank correlation method HWE was examined in controls by asymptotic Pearson’s chi-square test for each polymorphism in each study. The association between polymorphism and sport performance was estimated by means of odds ratios (OR) and corresponding 95% confidence intervals (CI) comparing athletes to controls. Meta-analyses were carried out using Comprehensive Meta-Analysis . Random effects models were used for meta-analysis, taking into account the possibility of heterogeneity between studies which was tested by the Q test and ITable S1Study identification: Included and excluded articles after full-text evaluation(DOC)Click here for additional data file.Table S2ACE & ACTN3 basic information: Basic information of included articles(XLS)Click here for additional data file.Table S3Sport discipline: Definition of sport discipline in included articles(DOC)Click here for additional data file.


The diagnostic yield of light blue crest(LBC) sign, which was observed by narrow band imaging with magnification endoscopy(NBI-ME), in detecting gastric intestinal metaplasia(IM) has shown variable results.We aimed to assess the diagnostic value of LBC under NBI-ME for detecting gastric IM.We performed a literature search of the Medline/PubMed, Embase, Web of Science, Science Direct and the Cochrane Library Databases; and a meta-analysis of pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and SROC area under the curve, using fixed- and random-effects models, for the accuracy of LBC-based IM diagnosis.We initially included 4 articles, but excluded 1 article to counter significant heterogeneity. When pooled, the remaining 3 articles, which included 247 patients with 721 lesions, showed the following patterns in IM diagnosis: sensitivity: 0.90 ; specificity: 0.90 (95% CI 0.86–0.93), positive likelihood ratio: 8.98 (95% CI 6.42–12.58), negative likelihood ratio: 0.12 (95% CI 0.09–0.16), and SROC area under the curve: 0.9560.As the studies varied by their definitions for positive LBC, endoscopy types, biopsy protocols, race of patient cohort, and physicians' proficiency, some sample sizes were limited so that subgroup analyses could not be performed.We concluded that observing LBC under NBI-ME is an accurate and precise means of diagnosing gastric IM. Gastric intestinal metaplasia (IM) is regarded as a precancerous lesion This meta-analysis aimed to assess the diagnostic accuracy, sensitivity, and specificity of LBC under NBI-ME in diagnosing gastric IM.Database searches were performed up to May 2013 in Medline/PubMed, Embase, Web of Science, Science Direct and the Cochrane Library, using two alternative search terms: “Narrow Band Imaging” and “intestinal metaplasia” and “diagnosis”; or “intestinal metaplasia” and “light blue crest”. References in available articles were also reviewed.Studies were selected according to the inclusion criteria: (1) aim of clarifying the accuracy of LBC in diagnosing gastric IM; (2) use of the Updated Sydney System Criteria or Chinese Consensus for the Diagnosis of Chronic Gastritis as pathological diagnostic criteria; (3) use of NBI-ME in all subjects, followed by the pathological examination; (4) use of “with or without LBC” as the standard to diagnose gastric IM under endoscopy; (5) recruitment of non-specific population for the study; (6) calculations for true or false-positive value, and true or false-negative value by directly or indirectly acquired LBC in gastric IM. We excluded studies (a) with specific populations or restricted age, gender or etiology; (b) reviews, lectures and comments; or (c) with no definite diagnostic criteria or diagnostic criteria that were incompatible with those in our study.+ if LBC was seen in any of the image fields, and otherwise as IM−LBC was defined as a fine, blue-white line on crests of epithelial surfaces/gyri, seen under NBI-ME IM was diagnosed according to the Updated Sydney System criteria. The diagnostic criteria of chronic gastritis in China are consistent with the Updated Sydney System criteria. Studies with these criteria were also included All included studies were assessed and data were extracted using a predefined data extraction form. The following variables were assessed: author, year and country of publication and endoscope type used. True positives, false positives, false negatives and true negatives were extracted using the histological findings as gold standard. The data were extracted both on a ‘per-patient’ and a ‘per-lesion’ basis wherever available.The quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool . The tooI2) for diagnostic odds ratio (DOR) were measured to estimate heterogeneity due to a non-threshold effect. When heterogeneity was present, a random-effects model was used for meta-analysis; otherwise, a fixed-effects model was used. Pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were calculated. Meta-DiSc software was used to delineate a symmetric receiver operator characteristic (SROC) curve from which the area under curve (AUC) was then calculated.Meta-DiSc (version 1.4) software was used to estimate heterogeneity due to threshold variation with Spearman correlation coefficient. Cochran's Q and inconsistency , which indicates a lack of definite threshold-effect-induced heterogeneity. The Cochran's Q and I2 for DOR were 21.99 (p = 0.0001) and 86.4% respectively, which indicates non-threshold-effect-induced heterogeneity. A random-effects model was used for meta-analysis. After analysis with the random-effects model, the pooled sensitivity was 0.86 (95% CI: 0.83–0.89), specificity was 0.88 (95% CI: 0.84–0.91), the positive likelihood ratio was 7.131 (95% CI: 4.39–11.59) and negative likelihood ratio was 0.15(95% CI: 0.08–0.30)  08–0.30) . SROC an08–0.30) .I2 for DOR were 1.02 (p = 0.5996) and 0% respectively, indicating that there was no heterogeneity among the remaining studies (721 samples from 247 patients). After analysis with a fixed-effects model, pooled sensitivity was 0.90 (95%CI: 0.86–0.92), specificity was 0.90 (95%CI: 0.86–0.93), positive likelihood ratio was 8.98 (95%CI: 6.42–12.58) and negative likelihood ratio was 0.12 (95%CI: 0.09–0.16) (The SROC curve showed that one study 09–0.16) , and AUC09–0.16) .As gastric IM is widely accepted as a precancerous lesion, its correct diagnosis and long-term follow up of subjects are important. Although the pathological criteria for IM in the Updated Sydney System criteria are regarded as a gold standard for its diagnosis, the accuracy of endoscopy for IM identification remains poor when using these criteria.Kaminishi et al. found that ash-colored nodular changes were specific (98–99%), but not sensitive (6–12%), for identifying histological intestinal metaplasia, and concluded that conventional endoscopy is unsuitable for diagnosing gastritis with IM As NBI-ME has been shown to reveal mucosal details, which may increase IM detection, the accuracy of LBC-based diagnosis of IM has been focus of several studies H. pylori eradication and chemoprevention, and endoscopic surveillance plays a key role Management of gastric IM includes endoscopic surveillance, Our meta-analysis show that LBC sign is accurate in diagnosing IM in gastric mucosa. However, its diagnostic value in Barrett's esophagus (BE) is unclear. One study showed LBC under NBI-ME to be 79% sensitive, 97% specific, and 89% accurate in diagnosing IM in BE There are some deficiencies in diagnosing of IM under NBI-ME in our study. First, no consensus on the diagnostic criteria of IM with LBC has been established. Of 9 references + patients. However, biopsy samples were not taken from adjacent non-LBC mucosa in the other two articles Although the diagnostic criteria and patient selection were strictly defined in the included studies, they showed obvious heterogeneity. One study from Thailand using ROC analysis showed evident bias The present meta-analysis has demonstrated that LBC under NBI-ME to be highly sensitive and specific in diagnosing gastric IM. This method can increase the accuracy of endoscopy for gastric intestinal metaplasia, guide endoscopic biopsy, and increase positive findings on pathological examination.Checklist S1(DOC)Click here for additional data file.


UCP) 1–3 polymorphisms and type 2 diabetes mellitus (T2DM). However, other studies have failed to confirm the associations. This paper describes a case-control study and a meta-analysis conducted to attempt to determine whether the following polymorphisms are associated with T2DM: -3826A/G (UCP1); -866G/A, Ala55Val and Ins/Del (UCP2) and -55C/T (UCP3).Some studies have reported associations between five uncoupling protein (UCP1–3 polymorphisms and T2DM. Pooled odds ratios (OR) were calculated for allele contrast, additive, recessive, dominant and co-dominant inheritance models. Sensitivity analyses were performed after stratification by ethnicity.The case-control study enrolled 981 T2DM patients and 534 nondiabetic subjects, all of European ancestry. A literature search was run to identify all studies that investigated associations between UCP polymorphisms did not differ significantly between T2DM and nondiabetic groups (P>0.05). Twenty-three studies were eligible for the meta-analysis. Meta-analysis results showed that the Ala55Val polymorphism was associated with T2DM under a dominant model ; while the -55C/T polymorphism was associated with this disease in almost all genetic models: allele contrast , additive  and dominant . However, after stratification by ethnicity, the UCP2 55Val and UCP3 -55C/T alleles remained associated with T2DM only in Asians . No significant association of the -3826A/G, -866G/A and Ins/Del polymorphisms with T2DM was observed.In the case-control study the frequencies of the UCP polymorphisms and T2DM; however, our meta-analysis detected a significant association between the UCP2 Ala55Val and UCP3 -55C/T polymorphisms and increased susceptibility for T2DM in Asians.In our case-control study of people with European ancestry we were not able to demonstrate any association between the  Diabetes mellitus (DM) has elevated prevalence, morbidity and mortality rates and the social and economic repercussions of its chronic complications compromise both the quality of life and productivity of those affected, making it a serious public health problem. Type 2 DM (T2DM) accounts for 90–95% of DM cases worldwide and usually occurs in obese subjects over 40 years of age. It is characterized by chronic hyperglycaemia caused by a combination of insulin resistance and inadequate compensatory insulin secretion Type 2 DM is a multifactorial condition and susceptibility to it is determined by the combined effects of multiple genetic and environmental factors Uncoupling proteins 1, 2 and 3 are members of an anion-carrier protein family located in the mitochondrial inner membrane Over the last few years, several studies have shown that UCPs reduce metabolic efficiency by dissociating substrate oxidation in mitochondria from ATP synthesis by the mitochondrial respiratory chain. This is thought to be accomplished by promoting net translocation of protons from intermembrane space, across inner mitochondrial membrane, to mitochondrial matrix, thereby dissipating the potential energy available for ATP synthesis and consequently reducing ATP production UCP loci and susceptibility to T2DM has been investigated in a number of genetic studies and particular attention has been focused on the -3826A/G (rs1800592) polymorphism in the promoter region of the UCP1 gene, the -866G/A polymorphism (rs659366) in the promoter region, the Ala55Val  polymorphism in exon 4 and the Ins/Del polymorphism, which is an insertion/deletion of 45 bp in the 3′ untranslated region (3′UTR) of exon 8 of the UCP2 gene, and the -55C/T (rs1800849) polymorphism in the promoter region of the UCP3 gene. The results of these studies are not uniform. While some of them have demonstrated associations between one or more of these polymorphisms and T2DM or related characteristics such as obesity, others were unable to detect any associations between the polymorphisms and such characteristics . Blood pressure (BP) was measured twice, in the sitting position, after a 5-min rest, and with a 2-min interval between measurements, using a mercury sphygmomanometer (Korotkoff phases I and V). The means of both measurements were used to calculate systolic and diastolic BP. Arterial hypertension was defined as BP ≥140/90 mm Hg, but patients on antihypertensive drugs were defined as hypertense irrespective of BP at the time of assessment.All patients had European ancestry . Ethnicity was defined by self-report. A standard questionnaire was used to collect information on age, age at DM diagnosis and drug treatment and all patients underwent physical examination and laboratory tests. They were weighed barefoot, wearing light outdoor clothing and their height was measured. Body mass index (BMI) was calculated as weight (kg)/height  was 7.18±2.05%, and mean BMI was 28.84±5.39 kg/mThe control group contained 534 nondiabetic volunteers attending the blood donation facility at the Hospital de Clínicas de Porto Alegre  . None of these people had DM or a family history of the disease. All of them had European ancestry.Serum samples were collected for laboratory testing after 12 hours fasting. Glucose levels were determined using the glucose oxidase method; GHb was assayed using an ion-exchange HPLC procedure ; and total plasma cholesterol, HDL-C, and triglycerides were all tested using enzymatic methods. The fraction of LDL cholesterol was calculated using the Friedewald equation. The nondiabetic subjects did not undergo any of these laboratory tests.UCP2 gene was detected by digesting polymerase chain reaction (PCR) products with the restriction enzyme MluI  as previously described UCP2 gene was detected by PCR using primers that have been described elsewhere DNA was extracted from peripheral blood leukocytes using a standardized salting-out procedure. The -866G/A (rs659366) polymorphism in the promoter region of the UCP2 gene, the -3826A/G (rs1800592) polymorphism in the promoter region of the UCP1 gene, and the -55C/T (rs1800849) polymorphism in the promoter region of the UCP3 gene. Reactions were conducted in 96-well plates, in a 5 µl total reaction volume using 2 ng of genomic DNA, TaqMan Genotyping Master Mix 1× (Life Technologies), and Custom TaqMan Genotyping Assay 1× specific for each polymorphism (Life Technologies). The plates were then placed in a real-time PCR thermal cycler  and heated for 10 minutes at 95°C, followed by 50 cycles of 95°C for 15 seconds and 63°C for 1 minute. Fluorescence data files from each plate were analyzed using automated allele-calling software .Primers and probes contained in the 40× Human Custom TaqMan Genotyping Assay  were used to genotype the Ala55Val (C/T) polymorphism (rs660339) in exon 4 of the Genotyping success rates were more than 95% for all polymorphisms and the calculated error rate based on PCR duplicates was less than 3%.2 tests. Allele and genotype frequencies were compared between groups using the χ2 test. Logistic regression analyses were performed to assess independent associations between the UCP polymorphisms and T2DM, after adjustment for age and gender. Two-tailed P values<0.05 were considered statistically significant. Statistical analyses were conducted using SPSS version 18.0 .Allele frequencies were determined by gene counting and departures from the Hardy-Weinberg equilibrium (HWE) were verified using goodness-of-fitness χUCP genes  using the following medical subject headings (MeSH): “Diabetes mellitus, type 2” AND  AND . The search was limited to human and English or Spanish language papers and was completed on August 24, 2012. All of the articles identified were also searched manually to identify any other relevant citations.This study was designed and described in accordance with current guidelines UCP polymorphisms in question between a known number of T2DM patients and nondiabetic subjects. Studies were excluded from the analysis if the genotype distributions in control group deviated from those predicted by the HWE, if they did not have sufficient data to estimate an OR with 95% CI or if they did not employ validated genotyping methods. If data were duplicated and had been published more than once, the most complete study was chosen.Two investigators (D.A.S and A.P.B.) independently reviewed the titles and abstracts of all articles selected in order to evaluate whether the studies were eligible for inclusion in the meta-analysis. Disagreements were resolved by discussion between them and when necessary a third reviewer (D.C.) was consulted. Where abstracts did not provide enough information regarding the inclusion and exclusion criteria, the full text of the article was retrieved for evaluation. We included observational studies  that compared one or more of the Data were independently extracted by two investigators (B.M.S. and L.A.B.) using a standardized abstraction form, and consensus was sought in all extracted items. When consensus could not be reached, differences in data extraction were resolved by a third reviewer (D.C.) and by referencing the original publication. The information extracted from each individual study was as follows: name of first author, publication year, ethnicity and number of subjects in case and control groups, age, gender, BMI, genotype and allele frequencies in case and control subjects and OR (95% CI).Two investigators (B.M.S and L.A.B.) independently assessed the quality of each eligible study using the Newcastle-Ottawa Scale (NOS) for assessing quality of case-control studies in meta-analysis 2 test. Gene-disease associations were measured using OR (95% CI) estimation based on the following genetic inheritance models: (1) allele contrast; (2) additive model; (3) recessive model; (4) dominant model and (4) co-dominant model Control subjects' genotype distributions were tested for conformity with HWE using a goodness-of-fitness χ2-based Cochran's Q statistic and inconsistency was assessed with the I2 metric. Heterogeneity was considered statistically significant at P<0.10 for the Q statistic and I2>50% for the I2 metric statistic. Where significant heterogeneity was detected, the DerSimonian and Laird random effect model (REM) was used to calculate OR (95% CI) for each individual study and for the pooled effect; where heterogeneity was not significant, the fixed effect model (FEM) was used for this calculation Heterogeneity was tested using a χUCP polymorphisms show different frequencies in different ethnic groups.Meta-regression and sensitivity analyses were carried out to identify key studies with a substantial impact on inter-study heterogeneity. The factors investigated by meta-regression were age, gender, BMI and ethnicity. Sensitivity analyses were performed after stratifying the studies by ethnicity given that the t test, as proposed by Egger, with P<0.10 considered indicative of statistically significant publication bias. All statistical analyses were performed using Stata 11.0 software .Risk of publication bias was assessed using funnel plot graphics, analyzed both visually and with the Begg and Egger test UCP1 -3826A/G, UCP2 -866G/A, UCP2 Ala55Val, UCP2 Ins/Del and UCP3 -55C/T polymorphisms. The genotype frequencies of all polymorphisms were in agreement with those predicted by the HWE in non-diabetic subjects (P>0.05) and did not differ significantly between T2DM and nondiabetic groups .UCP polymorphisms, but not the ones of interest here , 12 analyzed the UCP2 -866G/A polymorphism (4487/4229), 5 analyzed the UCP2 Ala55Val polymorphism (2112/1841), 3 analyzed the UCP2 Ins/Del polymorphism (1010/699), and 8 investigated the UCP3 -55C/T polymorphism (3370/3690). Table S2 lists the genotype and allele distributions and OR (95% CI) for the UCP polymorphisms in case and control samples from the different studies reviewed.Table S3 shows the quality of each individual study, assessed using the NOS scale. The highest quality studies were awarded nine stars. In general, most studies were considered as having good quality selection, comparability and exposure. None of the studies scored less than six stars and 47.8% of the studies had eight or nine stars.UCP polymorphisms and susceptibility to T2DM. Gene-disease associations were measured for the following genetic inheritance models: allele contrast, additive, recessive, dominant and co-dominant. UCP1 -3826A/G and UCP3 -55C/T polymorphisms and UCP2 polymorphisms and T2DM, both assuming the allele contrast model.UCP1 -3826A/G, UCP2 -866G/A or UCP2 Ins/del polymorphisms, irrespective of whether allele contrast, additive, recessive, dominant or co-dominant models of inheritance were used  (The 03–1.57) Table 2.UCP3 -55C/T polymorphism was significantly associated with T2DM when assuming allele contrast , additive  or dominant  models of inheritance. Additionally, a marginally significant association with T2DM was observed for the recessive  and co-dominant  models. Stratification by ethnicity showed that, when assuming an allele contrast model, the UCP3 -55T allele was associated with T2DM in Asians  but not in Europeans . In the same way, when assuming a dominant model, this polymorphism was associated with T2DM only Asians .The UCP polymorphisms when assuming the allele contrast model for the whole sample. Furthermore, significant heterogeneity was also observed between studies when assuming some of the other models of inheritance for these polymorphisms . Similarly, multivariate meta-regression analyses performed using these covariates also failed to explain the inter-study heterogeneity (data not shown).As can be observed in  I2>50%; Table 2.UCP2 Ala55Val, UCP2 Ins/Del and UCP3 -55C/T polymorphisms (data not shown). In contrast, two studies UCP2 -866G/A polymorphism. Heterogeneity was eliminated by exclusion of these two studies , but this did not significantly change the pooled OR . Similarly, heterogeneity among studies of the UCP1 -3826A/G polymorphism was effectively reduced  by exclusion of one study Sensitivity analyses were carried out in order to estimate the influence of each individual study on the meta-analysis results obtained when assuming allele contrast inheritance models by repeating the meta-analysis omitting a different study each time. Our results showed that no individual study significantly influenced the inter-study heterogeneity or the pooled ORs for the UCP polymorphisms analyzed (S2), which suggests that our data are statistically robust.No significant publication bias was detected in any of the inheritance models assessed for any of the UCP2 regulatory regions leading to increased expression could directly cause or exacerbate decreased glucose-stimulated insulin secretion, because of a reduced ATP/ADP ratio in pancreatic beta-cells and could therefore possibly contribute to the development of T2DM UCP1 -3826A/G, UCP2 -866G/A, UCP2 Ala55Val, UCP2 Ins/Del and UCP3 -55C/T polymorphisms in T2DM risk have been studied extensively, but the results of these association studies remain inconclusive , which is the mean OR obtained for the ≅20 genetic variants so far consistently associated with risk of T2DM UCP polymorphisms are very similar between T2DM patients and non-diabetic subjects, it seems unlikely that these variants could play an important role in the pathogenesis of T2DM in our population.Certain factors unrelated to the UCP1 -3826A/G, UCP2 -866G/A, UCP2 Ala55Val, UCP2 Ins/Del and UCP3 -55C/T polymorphisms on T2DM susceptibility, we conducted a meta-analysis of 22 published articles from different populations and also included the results from our case-control study. The results suggest that UCP1 -3826A/G, UCP2 -866G/A and UCP2 Ins/Del polymorphisms are not associated with risk of T2DM in the populations investigated. In contrast, when evaluating allele contrast and dominant models, the UCP2 55Val allele was associated with increased risk of T2DM in Asian samples but not in Europeans. Furthermore, the UCP3 -55T allele also was associated with risk to T2DM in Asian populations under allele contrast and dominant models.Meta-analysis has been considered a powerful tool for pooling the results from different studies that can overcome the problem of small sample sizes as well as inadequate statistical power of genetic association studies of complex traits UCP2 Ala55Val polymorphism appear to have a lower degree of uncoupling of the mitochondrial internal membrane, lower energy expenditure UCP3 -55C/T polymorphism has been associated with increased incidence of T2DM UCP genes and in other genes associated with T2DM and/or obesity.Subjects carrying the Val/Val genotype of the UCP3 gene UCP3 gene could be one of the PPAR-γ targets involved in the modulation of lipid metabolism and insulin sensitivity UCP3 mRNA expression than homozygotes for the -55C allele UCP3 mRNA levels have been associated with increased BMI in Pima Indians UCP3 mRNA expression in -55T allele carriers could explain the association between this polymorphism and lower BMI UCP3 -55C/T polymorphism on UCP3 expression.It is well known that functional polymorphisms can influence gene expression, regulating the final quantity of protein in a given tissue, or promote changes in protein activity. The -55C/T polymorphism is located 55 bp upstream of the most commonly used transcription initiation site of skeletal muscle UCP2 Ala55Val polymorphism causes a conservative amino acid change  at position 55 of exon 4 and, until now, there had been no evidence that this alteration generates a functional change in the protein UCP2 -866G/A polymorphism (|D′| = 0.991) UCP2 gene expression in a number of different tissues  was significantly associated with a greater risk of T2DM especially among overweight Caucasians. This haplotype was not constituted by any of the polymorphisms evaluated in our study. Third, because of the difficulty in getting the full texts of articles published in several languages, we only included studies published in English and Spanish. Fourth, heterogeneity is potentially a significant problem when interpreting the results of any meta-analysis of genetic association studies, and our meta-analysis showed significant inter-study heterogeneity in almost all genetic inheritance models tested. To investigate this issue in greater depth, meta-regression analyses were performed and showed that age, sex, BMI, and ethnicity did not made significant contributions to inter-study heterogeneity. The heterogeneity observed could be due to differences in sample selection, genotyping methods or gene-environment interactions and without detailed information on the metabolic and clinical characteristics of the studies reviewed we could not fully exclude the possibility that the heterogeneity observed might reduce our power to detect true associations. However, sensitivity analyses omitting one study at time did not significantly change the results for associations between the UCP polymorphisms and T2DM. Fifth, we also cannot rule out the possibility of type II error when analyzing associations between the UCP polymorphisms and T2DM after stratifying by ethnicity. For the whole sample, we had at least 80% power (α = 0.05) to detect even modest ORs (1.17–1.2) for almost all analyzed polymorphisms under the allele contrast model, which is an evidence that our results are robust. However, after stratification by ethnicity, we had 80% power to detect only OR ≥1.3 for all UCP polymorphisms .Despite all our efforts, we are aware that certain factors unrelated to the et al.UCP2 Ala55Val, UCP2 -866G/A and UCP3 -55C/T polymorphisms in 17 studies, but did not analyze neither the UCP1 -3826A/G and UCP2 Ins/Del polymorphisms nor the allele contrast or co-dominant inheritance models. These authors also failed to detect an association between the UCP2 -866G/A polymorphism and T2DM. In common with our meta-analysis, they also reported that the UCP3 -55C/T polymorphism was associated with T2DM in Asians when assuming an additive inheritance model , and in the overall population when assuming dominant  and recessive  models. Similarly, they found that the UCP2 Ala55Val polymorphism was associated with T2DM in Asians for the additive model , and in the overall population for dominant  and recessive  models.It is worth noting that our results are consistent with a previous meta-analysis conducted by Xu UCP2 Ala55Val and UCP3 -55C/T polymorphisms with T2DM only in Asian populations may be explained in part by the known differences in lifestyle and body weight distributions between Asian and Caucasian populations as well as differences in the genotype frequencies of the analyzed polymorphisms. Luan et al.UCP polymorphism on obesity and diabetes susceptibility.The association between the UCP1 -3826A/G, UCP2 Ins/Del and UCP2 -866G/A polymorphisms are not important risk factors for T2DM. However, our results strongly suggest that the UCP2 Ala55Val and UCP3 -55C/T are associated with susceptibility to T2DM, mainly in the Asian population. The absence of any associations of the five UCP polymorphisms and T2DM in our case-control study is in agreement with our meta-analysis results showing important associations of the UCP2 Ala55Val and UCP3 -55C/T polymorphisms with T2DM only in Asians. Further additional studies with larger samples are necessary to elucidate the roles possibly played by UCP polymorphisms in the pathogenesis of T2DM; particularly studies that analyze the effects of gene-gene and gene-environment interactions.In conclusion, our results indicate that the Figure S1Funnel plot for contrast allele model for UCP1 -3826A/G and UCP3 -55C/T polymorphisms.(TIF)Click here for additional data file.Figure S2Funnel plot for contrast allele model for UCP2 -866G/A, Ala55Val and Ins/Del polymorphisms.(TIF)Click here for additional data file.Table S1Characteristics of the eligible studies included in the meta-analysis.(DOCX)Click here for additional data file.Table S2Genotype and allele distributions of the UCP1 -3826A/G, UCP2 -866G/A, UCP2 Ala55Val, UCP2 Ins/Del and UCP3 -55C/T polymorphisms in patients with type 2 diabetes mellitus and nondiabetic subjects.(DOC)Click here for additional data file.Table S3Newcastle-Ottawa quality assessment scale for the studies included in the meta-analysis.(DOC)Click here for additional data file.


P = 0.0001,and OR = 1.36 (1.20–1.53), P < 0.0001, respectively. There was no similar association among AA participants (race interaction P = 0.0004for rs699 and P = 0.0001for rs5051). This research contributes to our understanding of the genetic basis of TRH, and further genetic studies of TRH may help reach the goal of better clinical outcomes for hypertensive patients.Treatment resistant hypertension (TRH) is defined as uncontrolled hypertension (HTN) despite the use of ≥3 antihypertensive medication classes or controlled HTN while treated with ≥4 antihypertensive medication classes. Risk factors for TRH include increasing age, diminished kidney function, higher body mass index, diabetes, and African American (AA) race. Importantly, previous studies suggest a genetic role in TRH, although the genetics of TRH are largely understudied. With 2203 treatment resistant cases and 2354 treatment responsive controls (36% AA) from the Genetics of Hypertension Associated Treatment Study (GenHAT), we assessed the association of 78 candidate gene polymorphisms with TRH status using logistic regression. After stratifying by race and adjusting for potential confounders, there were 2 genetic variants in the AGT gene  statistically significantly associated with TRH among white participants. The Met allele of rs699 and the G allele of rs5051 were positively associated with TRH: OR = 1.27 (1.12–1.44),  Multidrug resistance to blood pressure (BP) lowering treatments is a growing problem in the USA . In a reDemonstrated risk factors for TRH include increasing age, diminished kidney function, higher body mass index (BMI), diabetes mellitus (DM), and African American race . HowN = 39,114), an ancillary study to the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT included 42,418 hypertensive participants aged 55 years and older (46% women and 35% African American) who had one or more known CVD risk factors in addition to hypertension. ALLHAT was a randomized, double-blind, multicenter (n = 623 centers) clinical trial which tested whether the incidence of fatal CHD and nonfatal MI was lower with three antihypertensive drug classes  inhibitor, and an alpha-adrenergic blocker), compared to treatment using a thiazide-type diuretic. Participants were randomized to treatment in a ratio of 1 : 1 : 1 : 1.7 for amlodipine, lisinopril, doxazosin, and chlorthalidone, respectively, to optimize statistical power for the three primary comparisons of ALLHAT [These data were derived from the GenHAT study , 6.9% (n = 929) were classified as TRH cases and 5.3% (n = 719) were classified as easily-treated controls. Among the white participants with genotype data , 5.4%  were TRH cases and 6.9%  were controls. The extreme phenotype design has been shown to be an efficient and powerful approach for genetic discovery in complex disease , 15. TheThe BP values used to classify participants as TRH cases or controls were measured at the year-3 postrandomization clinic visit. Trained observers using standardized techniques measured SBP, defined as the first Korotkoff sound (1st phase), and DBP, defined as the reading at the last Korotkoff sound (5th phase). The measurements were taken only after the participant had been seated quietly for at least 5 minutes with feet flat on the floor and the arm at or as close to the level of the heart as possible. The cuff was deflated at a rate of 2 mm/sec until 10 mm Hg below the level of the diastolic reading was reached. Two measurements were taken, with at least a 30-second interval between the measurements, and recorded to the nearest even number. All BP measurements were calculated as the average of these two readings .Outcomes compared between TRH cases and controls were fatal CHD and nonfatal MI (hereafter referred to as “CHD”), stroke, heart failure , end-stage renal disease (ESRD), all-cause mortality, combined CHD , and combined CVD , with a mean follow-up of 4.9 years. Outcomes were reported by clinical investigators, and documentation  was submitted for any outcome involving hospitalization or death. Deaths occurring among participants lost to follow-up were also identified using national databases. Outcomes were not mutually exclusive; for example, the primary outcome (CHD) was included in the “combined CHD” outcome, and the combined CHD outcome (as well as stroke and CHF) was included in the “combined CVD” outcome, each outcome being more inclusive than the previous one. A detailed description of outcome ascertainment for ALLHAT has been previously published , 17, 18.DNA was isolated on FTA paper  from blood samples. Genotyping was performed for 78 candidate polymorphisms using amplified DNA products of a multiplex PCRs and detected using an immobilized probe research assay for multiple candidate markers  as described previously . These vP value of less than (0.05/156) = 0.00032 to be considered statistically significant. All statistical analyses were performed using STATA version 10.1 .To test for differences in baseline characteristics between TRH cases and controls in Baseline characteristics and follow-up BP measures for TRH cases and controls are shown in P < 0.001), heart failure , all-cause death , combined CHD , and combined CVD , but not stroke, among the African-American participants. There were also 28 incident ESRD events among the TRH group, and none among the control group for the African Americans. Among the white participants, TRH was positively associated with CHD , stroke , heart failure , ESRD , combined CHD , and combined CVD .P = 0.0001, and OR = 1.36 (1.20–1.53), P < 0.0001, respectively. There was no similar association among African-American participants, although it should be noted that the Met (M) allele of AGTM235T rs699 and the G allele of AGT-6 rs5051 are far less frequent among African-American than white participants. There was evidence of a significant interaction by race in the association of both AGTM235T rs699 and AGT-6 rs5051 with TRH when combining the data from whites and African-Americans (interaction P = 0.0004 for rs699 and P = 0.0001 for rs5051).Among the 78 genetic variants tested, there were no statistically significant genetic associations with TRH for the African-American participants after correcting for multiple comparisons. There were 2 genetic variants, both located in the angiotensinogen (AGT) gene, showing significant associations among white participants after adjusting for potential confounders and correcting for multiple comparisons: AGTM235T rs699 and AGT-6 rs5051 shown in . The MetP < 0.05) of association with TRH among both the African-American and white participant groups (see P = 0.002) and whites . For the matrix metalloproteinase-3 (MMP3) 5A/6A rs3025058 variant, however, the association with TRH differs between the races. For African Americans, the minor allele was protective , whereas for whites the minor allele confers higher odds of TRH . For the tumor necrosis factor (TNF) rs361525 variant, the minor allele (A) is positively associated with TRH among both African-Americans  and white participants . It should be noted that the frequency of the minor alleles for rs1801133, rs3025058, and rs361525 was much more common among white participants compared to African Americans  Thr allele was an independent risk factor for resistant hypertension. Although they did not report the racial make-up of the participant groups, the allele frequencies reported for their population were more similar to the GenHAT white group than the African-America group [AGT genetic variants are among the most studied in the context of hypertension and cardiovascular disease, and many studies have reported significant associations, the directions of the associations are not consistent [Two AGT genetic variants (rs699 and rs5051) were statistically significantly associated with TRH among the white participants, but no such associations were found for the African-American participants. This finding is in the opposite direction of a recent smaller study (70 TRH cases among Brazilian patients) showing that carriers of the ca group . Althougnsistent , 21–26. nsistent , 28, whiAlthough not statistically significant, it is of interest that 3 genetic variants  showed suggestive evidence of association with TRH among both the African-American and white populations. To varying degrees, all three of these genes have been previously studied in the context of hypertension. The matrix metalloproteinase (MMP) enzymes are inflammatory mediators that may contribute to hypertension, and though many previous studies which have shown an association with the C667T variant have found the minor T allele to be high risk, our data show the C allele to be more common among the TRH cases than the controls among both white and African-American participants. Previous studies have assessed the effect of MMP genes on hypertension and its sequelae, with an over expression of MMP found in hypertension –32. We or2 = 0.964 and r2 = 0.908 in the HapMap CEU population panel (Utah residents with Northern and Western European ancestry) and the HapMap YRI population panel , respectively. Both of these variants were in Hardy-Weinberg equilibrium (HWE) for our study population when tested in a race-specific manner .It is not surprising that both AGT rs699 and rs5051 show similar associations, as the AGT −6 and M235T variants are in tight linkage disequilibrium (LD) on chromosome 1. Using SNAP (SNP Annotation and Proxy Search) , the LD The strengths of this study include the relatively large number of TRH cases available in the ALLHAT/GenHAT study, including large numbers of African Americans with TRH. In addition, in the context of a randomized trial, we were better able to exclude pseudoresistant HTN cases characterized by poor BP measuring technique, nonadherence to medication, and/or inadequate dosing than a population-based study. In doing so, we observe a lower TRH prevalence in GenHAT versus other previous reports. Limitations of this case-control study include the loss of participants to death and other events, who might otherwise have been classified as TRH, as well as the inability to control for unknown differences between groups. In addition, ALLHAT recruited only patients aged 55 years and older, which does not allow for assessing the genetic effects on TRH among a younger population. Because a stronger genetic propensity may be present among those who manifest TRH at an early age, future prospective studies of the genetics of TRH would be well-advised to include a broad age range, including a younger hypertensive population. Improving prevention and treatment of TRH will be enhanced with a thorough knowledge of the genetic architecture of TRH. Understanding the underlying etiology and progression of this disorder can potentially generate new ideas for treatment. This research contributes to our understanding of the genetic basis of TRH, and further studies of TRH may help us reach the goal of better clinical outcomes for hypertensive patients.


RAD51 gene plays an important role in the pathogenesis of squamous cell carcinoma of the head and neck (SCCHN), colorectal cancer, ovarian cancer and acute leukaemia. A number of studies assessed the association between RAD51 135G/C polymorphism and the risk of these cancers in different population. However, the results have been inconclusive. We performed a systematic meta-analysis to evaluate the association between RAD51 135G/C polymorphism and the risk of these four types of cancer.RAD51 135G/C polymorphism and the risk of SCCHN, colorectal cancer, ovarian cancer and acute leukaemia published up to Oct 31, 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association.Pubmed, Cochrane library and Chinese Biomedical Literature Database (CBM) were searched for case-control studies on RAD51 135G/C polymorphism and the risk of the four types of cancers . However, there was a significant association between this polymorphism and SCCHN risk in the subgroup analysis by cancer type .A total of twenty-two published studies, with 6836 cases and 8507 controls were included. Overall, no significant association was found between RAD51 135G/C polymorphism was associated with the risk of SCCHN.The http://www.diagnosticpathology.diagnomx.eu/vs/1383180234106945.The virtual slide(s) for this article can be found here:  Cancer is one of the most common fatal diseases, which results from complex interactions between environmental and genetic factors . More anRAD51 gene is located on chromosome 15q15.1 in humans [RAD51 gene is essential for the repair of DNA damage. Growing evidences show that RAD51 has an irreplaceable role in the maintenance of genomic stability and the repair of DNA double-strand breaks [RAD51 genetic variations may contribute to the development of cancers [RAD51 gene [n humans . The RAD cancers . A functD51 gene  and has D51 gene .RAD51 135G/C polymorphism and risk of various cancers [RAD51 135G/C polymorphism and cancer risk have been inconclusive, partially because of the relatively small sample size of most studies. Therefore, we carried out this meta-analysis to evaluate the association between RAD51 135G/C polymorphism and risk of the four common types of cancers.Up to now, a variety of molecular epidemiological studies have been conducted to estimate the association between the  cancers -17, incl cancers -21, colo cancers -25, ovar cancers -28 and a cancers -37. HoweRAD51” AND “polymorphism” AND “(squamous cell carcinoma of the head and neck) OR  OR (ovarian cancer) OR (acute leukaemia)”. References of all identified studies and reviews were examined for additional articles.We conducted a comprehensive search in Pubmed, Cochrane library and Chinese Biomedical Literature Database (CBM), covering all articles published up to Oct 31, 2013, using the following terms: “RAD51 135G/C polymorphism and any of the four common cancers; (b) containing available genotype data in cases and controls for estimating an odds ratio (OR) and 95% confidence interval (CI); (c) genotype distributions of control population were consistent with Hardy-Weinberg equilibrium (HWE). The exclusion criteria were: (a) reviews, letters, editorial articles and case reports; (b) studies involving only a case population; (c) research not providing cancer information.Included studies in this meta-analysis met the following criteria: (a) a human case-control study on the association between Two investigators (Cheng and Shi) extracted the data from all of the eligible publications according to the inclusion and exclusion criteria mentioned above. Primary extraction data were reviewed by Zhen, and any disagreement was resolved by discussion among the three authors. From each study, the following information was collected: first author’s name, year of publication, study location, cancer type, sample size, source of control, the genotyping method, the number of genotype frequencies in cases and controls.RAD51 135G/C gene polymorphism and risk of the four cancers. The pooled ORs were performed for the homozygote comparison (G/G vs. C/C), heterozygote comparison (G/C vs. C/C), dominant (G/G + G/C vs. C/C) and recessive (G/G vs. G/C + C/C) genetic model comparison, and the significances of the summary ORs were determined by Z test, P < 0.05 was considered as statistically significant. The chi-square-based Q-test was used to assess the statistical heterogeneity among studies, and it was considered significant if P < 0.10 [P value greater than 0.10, indicating the absence of heterogeneity, then a fixed-effects model (the Mantel-Haenszel method) was applied to calculate the summary ORs [I2 was also calculated to test heterogeneity among included studies, with I2 < 25%, 25-75%, and >75% considered to represent low, moderate and high degree of heterogeneity, respectively [P < 0.05 was considered significant publication bias) was also used to evaluate the symmetry of the funnel plot [For each case-control study, we first examined whether the genotype frequencies in controls were consistent with HWE. ORs and 95% CIs were calculated as a measure of the association between the P < 0.10 . If the mary ORs . Otherwimary ORs . I2 was ectively . Sensitiectively , an asymnel plot . All of A total of 133 related publications were identified, of which 19 studies were not accepted since they were not full articles . Fifty-nine articles were not about the above four cancers, 33 publications were excluded because they did not meet the inclusion criteria . Finally, 22 studies including 6836 cases and 8507 controls were included in this meta-analysis . However, in the subgroup analysis by cancer type, there was a significant association between this polymorphism and SCCHN under homozygote comparison  . In the subgroup analyses of SCHNN and acute leukaemia, the I2 showed a low or moderate variation under all comparisons. In the subgroup analyses of colorectal cancer and ovarian cancer, under most comparisons, the moderate heterogeneity was detected. For source of controls, there was no significant heterogeneity under all comparisons of population-based case-control (PCC), except for heterozygous and dominant model comparisons  in hospital-based case-control (HCC). P value for heterogeneity was not significant under all comparisons in the subgroup analyses of Asian population, but in Caucasian group, there were high degree heterogeneity under heterozygous and dominant model comparisons .For the comprehensive analysis, the Sensitivity analyses were performed to assess the stability of the results in this meta-analysis. Statistically similar data were obtained after sequentially excluding each study, indicating that our results were statistically reliable.P = 0.248 for G/G vs. C/C)  and the Egger’s test did not show any evidence of publication bias  Figure . These dRAD51 gene is essential for the repair of DNA damage. A number of original studies have reported the association between RAD51 135G/C polymorphism and the risk of cancer with inconclusive results, These inconsistent results are possibly because of a small effect of the polymorphism on cancers risk or the relatively low statistical power of the published studies. To better understanding of this association,a meta-analysis, which potentially investigates a large number of individuals and could estimate the effect of a genetic factor on the risk of cancers, was needed to provid a quantitative approach for combining the results of various studies with the same topic, and for estimating and explaining their diversity [RAD51 135G/C polymorphism and risk of SCCHN, colorectal cancer, ovarian cancer and acute leukaemia.The RAD51 protein encoding by iversity ,45. We pRAD51 135G/C polymorphism and risk of SCCHN, colorectal cancer, ovarian cancer and acute leukaemia in any genetic model. However, in the subgroup analysis by cancer type, we found that the 135G/C polymorphism of the RAD51 gene was associated with a significantly increased SCCHN risk. There was an aggregated OR of 2.46 (95% CI = 1.08-5.61) for increased SCCHN susceptibility under homozygote comparison. This indicates that the RAD51 135G/C polymorphism may contribute to pathogenesis of SCCHN. GG genotype has been reported to enhance RAD51 gene transcription activity [The overall population analysis showed no significant association between activity -29,32,36RAD51 135G/C polymorphism and the risk of the four types of cancers were not detected.Heterogeneity is one of the important issues in performing a meta-analysis. In the present meta-analysis, heterogeneity was found in almost all comparisons. Using random-effect models and the stratified analyses by cancer type, sources of control and ethnicity, the heterogeneity was significantly decreased in most of the comparisons. The sensitivity analysis did not alter the results of our meta-analysis, indicating the results are stable. Meanwhile, the publication bias for the association between The present meta-analysis has some limitations. First, the control subjects were not uniformly defined. Selection bias and classification bias were possible because the included controls may have other different risks of developing cancers. Second, in the subgroup analyses, the sample sizes of Asian and African population were relatively small, not having enough statistical power to explore the real association. Third, cancer is a multi-factorial disease, our meta-analysis was based on unadjusted estimates.RAD51 135G/C was associated with a significantly increased risk of SCCHN. However, there was no significant association between this polymorphism and colorectal cancer, ovarian cancer or acute leukaemia susceptibility.In conclusion, the GG genotype of The authors have declared that no competing interests exist.DC performed the literature search, data extraction, statistical analysis and drafted the manuscript. HS, KZ and LY participated in data extraction. GZ supervised the literature search, data extraction, statistical analysis and drafted the manuscript. All authors read and approved the final manuscript.


There has been a decline in interest in general internal medicine that has resulted in a discrepancy between internal medicine residents’ choice in the R4 subspecialty match and societal need. Few studies have focused on the relative importance of personal goals and their impact on residents’ choice. The purpose of this study was to assess if internal medicine residents can be grouped based on their personal goals and how each group prioritizes these goals compared to each other. A secondary objective was to explore whether we could predict a resident’s desired subspecialty choice based on their constellation of personal goals.We used Q methodology to examine how postgraduate year 1–3 internal medicine residents could be grouped based on their rankings of 36 statements . Using each groups’ defining and distinguishing statements, we predicted their subspecialties of interest. We also collected the residents’ first choice in the subspecialty match and used a kappa test to compare our predicted subspecialty group to the residents’ self-reported first choice.Fifty-nine internal medicine residents at the University of Alberta participated between 2009 and 2010 with 46 Q sorts suitable for analysis. The residents loaded onto four factors (groups) based on how they ranked statements. Our prediction of each groups’ desired subspecialties with their defining and/or distinguishing statements are as follows: group 1 – general internal medicine (variety in practice); group 2 – gastroenterology, nephrology, and respirology (higher income); group 3 – cardiology and critical care ; group 4 – rest of subspecialties . There was moderate agreement (kappa = 0.57) between our predicted desired subspecialty group and residents’ self-reported first choice (p < 0.001).This study suggests that most residents fall into four groups based on a constellation of personal goals when choosing an internal medicine subspecialty. The key goals that define and/or distinguish between these groups are breadth of practice, lifestyle, desire to do procedures, length of training, and future income potential. Using these groups, we were able to predict residents’ first subspecialty group with moderate success. There is a discrepancy between societal need for general internal medicine specialists and internal medicine residents’ choice in the R4 subspecialty match -7. ThereThere have been several studies published examining demographic and non-demographic aspects associated with internal medicine residents’ choice of subspecialty ,12-21. HThe purpose of this study was to assess if internal medicine residents can be grouped based on their personal goals and how each group prioritizes these goals compared to each other. A secondary objective was to explore whether we could predict a resident’s desired subspecialty choice based on their constellation of personal goals.This study was conducted at the University of Alberta with postgraduate year (PGY) one to three internal medicine residents.The design framework was Q methodology invented in 1935 by British physicist-psychologist William Stephenson to allow quantitative analysis of subjective matters . Cross  describeWe began with all of the quotes from our previous qualitative study , and eacEthics approval for the study was granted by the Health Research Ethics Board – Panel B at the University of Alberta. With permission of the internal medicine residency program, we approached the PGY-1 to PGY-3 internal medicine residents at one of their Academic Half-Days at the start of the 2009 academic year to explain the project and ask for volunteers to participate in our study. Consenting participants were given randomly sorted cards, each with one of the 36 statements. They were first asked to rank the 36 statements into levels of agreement and disagreement. Each participant then entered the number corresponding to each statement onto the score sheet . The procedure was repeated at the start of the 2010 academic year to include residents who were not present at the 2009 session (those that missed the session and new residents to the program).As mentioned previously, Q Methodology uses a factor analysis, but instead of grouping items measuring a similar construct, it groups respondents who rank statements similarly. PQMethod 2.11  was usedOnce we had identified the number of factors, the same three independent evaluators examined each factor’s defining and distinguishing statements to predict the desired subspecialties of the residents that loaded onto a factor. To make these predictions, two of the evaluators (D.B.R. and N.K.) used their experiences as residency program directors for core internal medicine and general internal medicine respectively in which they counselled many residents on their selection of residency program, and the third evaluator (V.J.D.) used recent experiences as a resident and discussions with colleagues during training. Each evaluator predicted subspecialties for each factor, and then discussed their thoughts with any disagreements resolved by consensus. We used SPSS v.21  to calcuIn 2009, 43 residents participated with an additional 16 in 2010  out of a possible 114 residents. Thirteen Q sorts were excluded because of either missing or duplicate statements resulting in 46 Q sorts suitable for analysis. Residents were primarily 26 to 31 years old (63% of participants), with 16% younger than 26 years old and 21% older than 31 years old. The majority (63%) were female, and 42% were in PGY-1, 28% in PGY-2 and 30% in PGY-3. Nine percent of participants did not have a premedical degree, 63% had a bachelor’s degree and 28% had a master’s degree. Participants desired choice of subspecialties is shown in Figure We compared the different solutions from rotating three to six factors in terms of number of Q sorts that loaded onto a factor and percentage of variance explained ; “My decision was predominantly based on experiences as a medical student” (mild disagreement from the four factors); and “Prestige and respect from colleagues matters to me” . The three statements with the most disagreement between factors were: “I am willing to do as many years as it takes to get the job and subspecialty I want” ; “I like a little bit of everything and variety” ; and “A two-year GIM fellowship is a deterrent” (mild agreement from factor 2 but disagreement from other factors).The three evaluators reviewed the defining and distinguishing statements  to one of four groups. Using these personal goals groups, we had moderate agreement (kappa = 0.57) between our predicted subspecialty group and residents’ self-reported first desired subspecialty, something that we have not seen in our review of the literature.The main advantage of Q methodology is that it forces a quasi-normal distribution so respondents cannot select the same response for every item, as they can with traditional survey methods. Horn and colleagues’  CanadianExamining the four groups of residents  of the 114 eligible residents; however, 13 did not complete the Q sort successfully. This resulted in only 46 participants of whom 11 did not load onto a factor and one did not complete their desired subspecialty, so they could not be included in our prediction of subspecialty compared to self-reported desired subspecialty. Though the demographics of the remaining 34 participants appear similar to the rest, this reduction in participants may reduce the generalizability of our findings. Finally, the statements used, though diverse, did not incorporate every possible personal goal such as desire for long versus short-term relationships with patients, debt load when entering residency, interest in specific issues such as health care policy, or desire for an academic versus non-academic career.A future Q methodology study could involve residents across Canada, which might allow us to get at a more granular level . Future research could also incorporate personal goals that were missing from this study, and could be done in a computerized format to prevent missing data. This would be helpful to further elucidate the impact of personal goals on residents’ choice in the R4 subspecialty match.Although previous aspects identified in the literature are important, this study suggests that residents fall into four groups based on a constellation of personal goals when choosing an internal medicine subspecialty. The key goals that define and/or distinguish between these groups are breadth of practice, lifestyle, desire to do procedures, length of training, and future income potential. Using these personal goals groups, we were able to predict residents’ first subspecialty choice/group with moderate success.The authors declare they have no competing interests, financial or other.All authors listed have contributed sufficiently to the project to be included as authors, and all those who are qualified to be authors are listed in the author byline. NK conceived the original idea for the project. VJD worked on the design of the project with the input of NK. VJD carried out the data collection and analysis. VJD drafted the first version and subsequent revisions of the manuscript; NK reviewed and edited the various versions of the manuscript. Both authors approved the final draft.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6920/13/171/prepub


Several large, rare chromosomal copy number variants (CNVs) have recently been shown to increase risk for schizophrenia and other neuropsychiatric disorders including autism, ADHD, learning difficulties and epilepsy.We wanted to examine the frequencies of these schizophrenia-associated variants in a large sample of individuals with non-psychiatric illnesses to better understand the robustness and specificity of the association with schizophrenia.We used Affymetrix 500K microarray data from 10,259 individuals from the UK Wellcome Trust Case Control Consortium (WTCCC) who are affected with six non-psychiatric disorders  to establish the frequencies of nine CNV loci strongly implicated in schizophrenia, and compared them with the previous findings.Deletions at 1q21.1, 3q29, 15q11.2, 15q13.1 and 22q11.2 (VCFS region), and duplications at 16p11.2 were found significantly more often in schizophrenia cases, compared with the WTCCC reference set. Deletions at 17p12 and 17q12, were also more common in schizophrenia cases but not significantly so, while duplications at 16p13.1 were found at nearly the same rate as in previous schizophrenia samples. The frequencies of CNVs in the WTCCC non-psychiatric controls at three of the loci  were significantly higher than those reported in previous control populations.The evidence for association with schizophrenia is compelling for six rare CNV loci, while the remaining three require further replication in large studies. Risk at these loci extends to other neurodevelopmental disorders but their involvement in common non-psychiatric disorders should also be investigated. Since 222.1We studied data from 10,259 individuals that passed quality control filtering. Subjects were ascertained by the WTCCC with coronary artery disease , Crohn's disease , hypertension , rheumatoid arthritis , type 1 diabetes  and type 2 diabetes . They are of White European ancestry and live in the UK. Extensive information about the samples and method of genotyping has been published previously . The WTC2.2Genotyping was performed with Affymetrix 500K arrays that cover the genome with ~ 500,000 single nucleotide polymorphisms (SNPs), as described previously . The sigPreviously we performed similar CNV analyses on other phenotypes from the WTCCC dataset  . All theAll chromosomal positions presented in this paper are according to NCBI Build 36 (hg18), March 2006 of the UCSC Genome Browser.2.3NRXN1 gene, also implicated as a risk factor for schizophrenia, , therefore a comparison with another large sample of controls from another country appeared to be justified.Several large CNVs have previously received strong replicated support for association with schizophrenia: deletions at 1q21.1 , 2p16.3,XN1 gene , 3q29 .Here we studied a sample of 10,259 individuals from the UK, affected with several common non-neuropsychiatric disorders. This dataset allowed us to assess the frequency of these CNVs in an independent sample of comparison subjects. These individuals have not been screened for the presence of schizophrenia or other CNV-related neurodevelopmental disorders. Nevertheless, the prevalence of schizophrenia is only about 1% in the general population, and therefore the use of unscreened reference samples is not expected to make an appreciable difference to the results. Even if 100 of the ~ 10,000 controls have schizophrenia (~ 1%), these will not contribute more than two or three CNVs in total from those listed in Overall six of the loci remain significantly more common in the subjects affected with schizophrenia, compared to the WTCCC reference set . This is despite the fact that the new comparison sample is ~ 4 times smaller than the previously used combined control samples. This provides strong additional support that these CNVs are true risk factors for schizophrenia. For the remaining three loci  the differences were not statistically significant , with a The difference between the control/ reference sets, and the observations that the rates of CNVs at 16p13.1, 17p12 and 17q12 were not statistically different between schizophrenia cases and the non-psychiatric WTCCC reference set suggest that either these CNVs also increase the risk to develop some of the disorders that comprise the WTCCC sample, or that the odds ratios in the original studies were inflated, or even false-positives, or that the use of the smaller set of controls here is underpowered. In The decrease of the estimated odds ratios for several loci in the new analysis could be also due to the bias known as the “winner's curse” . This arWe will now discuss how the current results relate to previous findings for each locus.4.1− 5).This 1.4 Mb deletion contains 11 genes and was found to be associated with schizophrenia in the three largest CNVs surveys . It has 4.2Deletions of 3q29, spanning 1.4 Mb and 21 genes, were first reported to be associated with schizophrenia by 4.3The first report of an association between the 0.6 Mb deletions at this locus that span four genes, and schizophrenia was made by 4.4The association with schizophrenia of this 1.5 Mb deletion that spans seven genes, is supported by the three largest studies in schizophrenia . The same duplication is also a risk factor for autism, while the reciprocal deletion of this locus is associated with autism and developmental delay   , while t− 5) . These r− 5) .4.8HNF1B, has been implicated in the renal cysts and diabetes (RCAD) syndrome  and other neurodevelopmental disorders.Deletions of 2.4 Mb at this locus constitute a known genomic disorder, 22q11.2 Deletion Syndrome, also known as Velo-Cardio-Facial Syndrome (VCFS) or DiGeorge Syndrome . This waThe current study provides further support for the involvement of deletions at 1q21.1, 3q29, 15q11.2, 15q13.3, 22q11.2 and duplications at 16p11.2 as risk factors for schizophrenia. The evidence implicating deletions at 17p12 and 17q12 and especially duplications at 16p13.1 is weaker and needs further study. All of these loci have also been shown to increase risk for other neuropsychiatric disorders, indicating that these rare, large DNA variants are not phenotype-specific. Furthermore, most carriers of these CNVs do not develop schizophrenia (i.e. they have a limited penetrance for this disorder of 2–7.4%), with the exception of the deletion at 22q11.2 that has an estimated penetrance of 55% .An important limitation of our study is that most of these CNVs cause other medical disorders and therefore could be found among cohorts recruited for other conditions. This could explain why the rate in the WTCCC comparison subjects was higher than in previously analysed controls for several of these loci. While the overall burden of these CNVs appears to be the same in the WTCCC non-psychiatric reference set and ~ 3000 controls (see above), this study has no statistical power to estimate if any individual non-psychiatric disorder in the WTCCC has an increased burden of any single CNV locus discussed here. Judging from the experience in schizophrenia, such associations have to be tested on > 5000 cases from each phenotype.Wellcome Trust under awards Funding for the project was provided by the Dr. Grozeva performed quality control of the data, analysed the data and wrote the first draft of the manuscript. The Wellcome Trust Case Control Consortium compiled the dataset . Drs Conrad, Barnes and Hurles generated the CNV calls using the SNP Affymetrix intensity data and compiled the list of filtered CNV calls. Dr. Kirov initiated the current analysis. Profs Craddock, O'Donovan and Owen contributed to the planning of the study and the writing of the manuscript. All authors edited and approved the final version of the manuscript.None.


Jatropha curcas seed oil by urea complexation. Urea complexation is a method used by researchers to separate fatty acids (FAs) based on their molecular structure. Effects the ratio of urea-to-FAs, crystallization temperature and crystallization time on the final products of urea complexation were examined. D-optimal Design was employed to study the significance of these factors and the optimum conditions for the technique were predicted and verified.This study was done to obtain concentrated polyunsaturated fatty acid (PUFA) linoleic acid  and monounsaturated fatty acid (MUFA) oleic acid  from Optimum conditions of the experiment to obtain maximum concentration of LA were predicted at urea-to-FAs ratio (w/w) of 5:1, crystallization temperature of −10°C and 24 h of crystallization time. Under these conditions, the final non-urea complex fraction (NUCF) was predicted to contain 92.81% of LA with the NUCF yield of 7.8%. The highest percentage of OA (56.01%) was observed for samples treated with 3:1 urea-to-FAs ratio (w/w) at 10°C for 16 h. The lowest percentage of LA (8.13%) was incorporated into urea complex fraction (UCF) with 1:1 urea-to-FAs ratio (w/w) at 10°C for 8 h.The separation of PUFA (LA) and MUFA (OA) described here. Experimental variables should be carefully controlled in order to recover a maximum content of PUFA and MUFA of interest with reasonable yield% with a desirable purity of fatty acid of interest. The high content of LA makes Jatropha curcas seed oil very important for industry use. LA can be used in protective coatings, plastics, surfactant, dispersants, biolubricant, and a variety of synthetic and in the preparations of other long chain compounds. The high content of LA in seed oil of J. curcas is very important to the production of oleo-chemicals , SFAs  Y2 in %], MUFA (OA) Y3 in %] and PUFA (LA) Y4 in %] are shown in equations 1, 2, 3 and 4 respectively. The yield of UCF Y5 in %], SFAs  Y6 in %], MUFA (OA) Y7 in %] and PUFA (LA) Y8 in %] after urea inclusion fractionation are shown in equations 5, 6, 7 and 8 respectively. An initial screening step was carried out using the technique describe by [A three-factor D-optimal design was employed to study the responses, after urea inclusion fractionation. The yield of NUCF X1, X2 and X3 representing the urea-to-FAs ratio (w/w), crystallization temperature (°C), and crystallization time (h). The settings for the independent variables were low and high values: urea-to-FAs ratio of 1 and 5; crystallization temperature of −10 and 10 and crystallization time of 8 and 24. Each variable was coded at three levels: -1, 0, and +1. A quadratic polynomial regression model was assumed for predicting individual Y variables. The model proposed for each response of Y was:The independent variables were B0; Bi; Bii and Bij are constant, linear, square and interaction regression coefficient terms, respectively, and xi and xj are independent variables. The goodness of fit of the model was evaluated by the coefficient of determination R2 and the analysis of variance (ANOVA).Where The authors declare that they have no competing interests.JS developed the concept, analyzed the data and drafted the manuscript. BMA performed the separation method, optimization study and statistical analysis. NS advised on the methods of tests. All authors read and approved the final manuscript.


This study was designed to determine the glycemic indices of five commonly used varieties of dates in healthy subjects and their effects on postprandial glucose excursions in individuals with type 2 diabetes mellitus.Composition analysis was carried out for five types of dates (Tamer stage). The weights of the flesh of the dates equivalent to 50 g of available carbohydrates were calculated. The study subjects were thirteen healthy volunteers with a mean (± SD) age of 40.2 ± 6.7 years and ten participants with type 2 diabetes mellitus (controlled on lifestyle measures and/or metformin) with a mean HbA1c (± SD) of 6.6 ± (0.7%) and a mean age (± SD) of 40.8 ± 5.7 years. Each subject was tested on eight separate days with 50 g of glucose (on 3 occasions) and 50 g equivalent of available carbohydrates from the 5 varieties of date (each on one occasion). Capillary glucose was measured in the healthy subjects at 0, 15, 30, 45, 60, 90 and 120 min and for the diabetics at 0, 30, 60, 90, 120, 150 and 180 min. The glycemic indices were determined as ratios of the incremental areas under the response curves for the dates compared to glucose. Statistical analyses were performed using the Mann-Whitney U test and repeated measures analysis of variance.p = 0.83).Mean glycemic indices ± SEM of the dates for the healthy individuals were 54.0 ± 6.1, 53.5 ± 8.6, 46.3 ± 7.1, 49.1 ± 3.6 and 55.1 ± 7.7 for Fara'd, Lulu, Bo ma'an, Dabbas and Khalas, respectively. Corresponding values for those with type 2 diabetes were very similar . There were no statistically significant differences in the GIs between the control and the diabetic groups for the five types of dates, nor were there statistically significant differences among the dates' GIs (df = 4, F = 0.365, The results show low glycemic indices for the five types of dates included in the study and that their consumption by diabetic individuals does not result in significant postprandial glucose excursions. These findings point to the potential benefits of dates for diabetic subjects when used in a healthy balanced diet.NCT01307904ClinicalTrials.gov  Phoenix dactylifera L.) is one of mankind's oldest cultivated plants. There are more than 2000 different varieties of dates [The date palm , salts, minerals, vitamins, fatty acids (0.2-0.5%), proteins 2.3-5.6%), and fibers (6.4-11.5%) [%, and fiThe daily consumption of dates is a deeply rooted tradition in many societies, including those in the UAE. In Oman, which lies immediately adjacent to the UAE, the per capita daily consumption of dates is estimated at 55-164 grams and thus constitutes a vital component of the daily diet . The UAEThe prevalence of diabetes mellitus (DM) in the UAE is currently the second highest in the world according to the International Diabetes Federation 2010 . From a It is well documented that adherence to a healthy diet can improve glycemic control , may redThe glycemic index (GI), first proposed in 1981 , is a syIn the UAE, the partaking in frequent snacks of dates (as often as four to five times per day) is a tradition. Our observation from clinical practice is that diabetic patients tend to receive conflicting messages from health educators regarding the advisability of consuming dates, with some suggesting restraint or even avoidance as a means to improve glycemic control. However, this appears to conflict with findings from previous studies demonstrating that dates have low to medium GIs ,21-24. Wc ≤ 8%) on diet with or without metformin. Exclusion criteria for both healthy and diabetic volunteers included morbid obesity (BMI > 40 kg/m2), pre diabetes, pregnancy, presence of gastroenterological disorders, alimentary tract surgery, a history of gastroenteritis in the prior six months, any alcohol intake, smoking, taking any medications (except metformin), poorly controlled diabetes (HbA1c > 8%) and the presence of chronic diseases  or acute illness (such as upper respiratory tract or urinary tract infection).Study participants were recruited from local poster advertisements Figure . After pThirteen healthy subjects  and ten volunteers with type 2 DM  were enrolled for the study Table . These nFara'd, Lulu, Bo ma'an, Dabbas and Khalas, five varieties of date, very popular in the UAE, were chosen for this study. The same batches of packaged dates (Tamer stage) obtained from a local dates processing factory  were used for all tests. The compositions of the dates Tables , 3 were ® Lifescan glucometers , which were tested for accuracy and precision with the provided kits and against a Beckman Synchron CX7 laboratory analyzer  which uses the glucose oxidase method. The coefficient of variation was 2.20-2.65% for both glucometers using three testing samples across the low, mid and high glucose ranges.Glucose was measured in capillary blood samples using one of two One Touch II® 50, Thermo Scientific) followed sequentially by 50g carbohydrate equivalents of the five selected dates , and consumed by all participants with 250 ml of water. Blood glucose was monitored during 2 hrs for the healthy individuals at 0, 15, 30, 45, 60, 90 and 120 min and over 3 hrs for the diabetics at 0, 30, 60, 90, 120, 150 and 180 min . Areas uThe study conformed to the requirements of the Declaration of Helsinki and was approved by Al Ain Medical District Human Research Ethics Committee  and was registered in a clinical trials registry .Data were analyzed using Microsoft Excel 2003 and SPSS version 18 . For each dates meal the GI was measured by calculating the area under the curve using the formulae kindly provided by Professor Thomas Wolever from the University of Toronto-Canada. Standard descriptive statistics were used and results are presented as means and standard deviations (SD) or standard errors of the mean (SEM). In addition, for each type of date the GIs were compared between DM patients and controls using Mann-Whitney tests. Comparisons of GIs of the 5 different dates were carried out using repeated measures analysis of variance (ANOVA) on the combined (DM and controls) data set using groups as a between subjects factor. In all cases the statistical significance level was set at p ≤ 0.05.The composition of the dates studied is shown in Table 2, and 10 subjects with type 2 diabetes (F:M = 1:1) with a mean age (± SD) of 40.8 ± 5.7 years, BMI (±S D) of 30.7 ± 5.2 kg/m2 and mean HbA1c (± SD) of 6.6 ± 0.7  with a mean (± SD) age of 40.2 ± 6.7 years and BMI (± SD) of 27.4 ± 4.1 kg/mTable There were no statistically significant differences in the GIs between the DM and control groups (M-W tests), for any of the 5 dates, with p-values of 0.457, 0.495, 0.352, 0.951 and 0.901 for Farad, Lulu, Bo ma'an, Dabbas, and Khalas respectively. Nor was there significant heterogeneity in GIs among the 5 types of dates tested in GIs, ANOVA;  within and between healthy and diabetic subjects. Given the absence of any evidence for heterogeneity in GIs among dates, no further post-hoc pairwise comparison were carried out. Figures Dates are rich in certain nutrients and are widely consumed in many countries, particularly those within the Islamic world. They have been directly referred to in the Qur'an and in the Hadith (sayings of the Holy Prophet Mohammed).Composition analysis of the pulp of the dates in our study was in keeping with the previously published literature ,4,28. ThThe dietary fiber content varies depending on the type and degree of ripeness -6. The pThe tested dates contain a higher percentage of protein than common fruits such as apples, oranges, bananas and grapes which contain 0.3%, 0.7%, 1.0% and 1.0% protein, respectively . Our datThe range of GIs of the five types of dates assessed in our study was 46 to 55 for healthy subjects and 43 to 53 for the type 2 diabetic patients. All of these date varieties, therefore, are low GI food items. In healthy subjects, the mean GIs reported by Miller et al for Khalas and Bo ma'an were 35.5 and 30.5 respectively  and the A diet low in GI may decrease the risk of coronary heart disease, gallbladder disease and breast cancer. Furthermore, a low GI diet demonstrably improves HbA1c levels, body weight and the lipid profile ,15-43.Whereas our estimates of the GIs among healthy volunteers are similar to previously reported values ,22,34, wThe test meals were not randomized and, ideally, the glucose meals should have been taken before, halfway and at the end of the test meals. We used only five varieties of dates (Tamer stage) hence the conclusions from this study may not be generalizable to all types of dates. The volunteers with type 2 DM were controlled on diet or metformin only. Thus, the results of this study cannot be extended to all patients with type 2 DM especially at advanced stages of the disease, i.e. those receiving multiple oral hypoglycemic agents or insulin.We have determined the composition of five common types of dates  and calculated their glycemic indices. Our results support the study hypothesis that the tested varieties of dates would have low GIs in healthy subjects and that their consumption by diabetic individuals does not result in significant postprandial glucose excursions. Future prospective studies are needed to evaluate the effects of long-term consumption of these dates on prevention of diabetes and other chronic diseases in the UAE, and on the control of hyperglycemia in subjects with diabetes.GI: Glycemic Index; HbA1c: Glycated hemoglobin A1c; OGTT: Oral glucose tolerance test.The authors declare that they have no competing interests.AJ was the principal author, PI of the study, conceptualized and supervised the study, participated in the study design, analysis and interpretation of data and writing of the manuscript. BA participated in the study design and made substantial contributions to subjects' recruitment and performed laboratory and data analysis and co-wrote the paper. HS and SG participated in the design of the study and writing of the manuscript. SA and MG participated in the date's composition analysis. All authors read and approved the final manuscript.