atrial fibrillation ( af ) is the most common sustained arrhythmia   encountered in clinical settings .
it is associated with higher risk of mortality , accounting for approximately 12% of all deaths in the general population .
the prevalence of af increases substantially with age , affecting around 10% of people over 80 years old .
about 0.77% of the chinese population have af . however , the exact pathogenesis of af is still unclear .
af is usually considered to be affected by multiple cardiovascular risk factors , including advancing age , male sex , hypertension , diabetes , ischemia , valvular heart disease , left ventricular ( lv ) dysfunction , heart failure , and obesity .
furthermore , studies have reported that genetic factors play important roles in the pathogenesis of af , such as kcna5 , kcnq1 , kcne2 , and nup155 .
caveolin-1 gene ( cav1 ) encodes a caveolae protein , usually expressed in atrial myocytes .
recent genome - wide association studies ( gwas )   have reported that a single - nucleotide polymorphism ( snp ) , rs3807989 , in cav1gene was associated with the susceptibility to af , and the association of this snp with af risk has been replicated in several populations .
olesen et al .   demonstrated that variants of rs3807989 in cav1gene are associated with af independent of traditional cardiac risk factors in caucasians .
however , the findings from the study of li et al .   conflict with the results above ; they showed that the snp rs3807989 in cav1 gene may not be a risk factor for af in the chinese han population . in view of this disagreement
, it was necessary to perform a meta - analysis to determine the association of cav1 rs3807989 polymorphism with the risk of af in the present study .
we searched for studies about the association of cav1 rs3807989 polymorphism with the risk of af in the electronic databases pubmed , medlin , and web of science before august 20 , 2015 .
rs3807989  or  polymorphism  or  7q31  and  atrial fibrillation ( af )  . only studies conducted in humans were included .
concurrently , we manually reviewed the references of reviews to search for additional relevant articles .
if the same population was replicated in over 1 publication , only the most recent study with complete data was included in this meta - analysis .
the inclusion criteria were : 1 ) cohort or case - control studies ; 2 ) studies about the association between the cav1 rs3807989 ( g / a ) polymorphism and risk of af ; 3 ) studies that provide detailed genetic frequency data ( aa , ga , and gg ) in af cases and controls for extraction ; 4 ) studies published in english ; and 5 ) distribution of genotype in controls was in accord with hardy - weinberg equilibrium ( hwe ) .
the exclusion criteria were : 1 ) duplicated studies ; 2 ) studies not conforming to hwe ; and 3 ) incomplete raw data . in case of disagreement on the quality scores between the 2 reviewers , differences were resolved through discussion and consultation with a third reviewer .
the following information was extracted from each selected study : name of the first author , year of publication , ethnicity , sample size , age , sex , incidence of hypertension and coronary artery disease , af type , and genotypic distribution of in cases and controls .
the quality of each selected study was assessed by 2 reviewers using the newcastle - ottawa scale ( nos ) quality system .
genotypic distribution of the controls from selected studies was assessed using hwe with fisher s exact test .
all statistical analyses were conducted using stata statistical software 12 . in the current meta - analysis , 5 genetic models 
allelic model ( g versus a ) , recessive model ( aa versus ga + gg ) , dominant model ( ga + aa versus gg ) , homozygous ( gg versus aa ) , and heterozygous genetic models ( gg versus ga )  were used to confirm the relationship of cav1 rs3807989 polymorphism with the risk of af using the combined odds ratios ( ors ) with corresponding 95% confidence intervals ( cis ) . the q - test and the i statistic ( range , 0100% )
if p<0.1 or i > 50% , the study would be judged to have significant heterogeneity and the random - effects model was used to estimate the pooled or ( dersimonian and laird methods ) ; otherwise , the fixed - effects model was used ( the mantel - haenszel method ) .
publication bias was estimated using begg s funnel plot . funnel plot asymmetry was determined by egger s linear regression test .
we searched for studies about the association of cav1 rs3807989 polymorphism with the risk of af in the electronic databases pubmed , medlin , and web of science before august 20 , 2015 .
rs3807989  or  polymorphism  or  7q31  and  atrial fibrillation ( af )  . only studies conducted in humans were included .
concurrently , we manually reviewed the references of reviews to search for additional relevant articles .
if the same population was replicated in over 1 publication , only the most recent study with complete data was included in this meta - analysis .
the inclusion criteria were : 1 ) cohort or case - control studies ; 2 ) studies about the association between the cav1 rs3807989 ( g / a ) polymorphism and risk of af ; 3 ) studies that provide detailed genetic frequency data ( aa , ga , and gg ) in af cases and controls for extraction ; 4 ) studies published in english ; and 5 ) distribution of genotype in controls was in accord with hardy - weinberg equilibrium ( hwe ) .
the exclusion criteria were : 1 ) duplicated studies ; 2 ) studies not conforming to hwe ; and 3 ) incomplete raw data .
in case of disagreement on the quality scores between the 2 reviewers , differences were resolved through discussion and consultation with a third reviewer .
the following information was extracted from each selected study : name of the first author , year of publication , ethnicity , sample size , age , sex , incidence of hypertension and coronary artery disease , af type , and genotypic distribution of in cases and controls .
the quality of each selected study was assessed by 2 reviewers using the newcastle - ottawa scale ( nos ) quality system .
genotypic distribution of the controls from selected studies was assessed using hwe with fisher s exact test .
all statistical analyses were conducted using stata statistical software 12 . in the current meta - analysis , 5 genetic models 
allelic model ( g versus a ) , recessive model ( aa versus ga + gg ) , dominant model ( ga + aa versus gg ) , homozygous ( gg versus aa ) , and heterozygous genetic models ( gg versus ga )  were used to confirm the relationship of cav1 rs3807989 polymorphism with the risk of af using the combined odds ratios ( ors ) with corresponding 95% confidence intervals ( cis ) . the q - test and the i statistic ( range , 0100% )
if p<0.1 or i > 50% , the study would be judged to have significant heterogeneity and the random - effects model was used to estimate the pooled or ( dersimonian and laird methods ) ; otherwise , the fixed - effects model was used ( the mantel - haenszel method ) .
publication bias was estimated using begg s funnel plot . funnel plot asymmetry was determined by egger s linear regression test . a p value less than 0.05 was considered statistically significant .
a total of 4 articles [ 5,1719 ] involving the association of cav1 rs3807989 polymorphism with af risk were selected in this meta - analysis , including 3758 af cases and 6126 controls . a detailed flow diagram of the search process for this meta - analysis is displayed in figure 1 .
table 1 shows the main characteristics of the selected studies and the characteristics of included patients are listed in table 2 .
as shown in figure 2 , all 5 comparisons revealed the association between cav1 rs3807989 polymorphism and af risk after meta - analysis with fixed- or random - effects models : allelic model ( g / a ; or=1.228 , 95%ci : 1.0611.420 ; p=0.006 ) , homozygote model ( gg / aa ; or=1.439 , 95%ci : 1.0941.894 ; p=0.009 ) , heterozygote model ( gg / ga ; or=1.257 , 95%ci : 1.0641.486 ; p=0.007 ) , dominant model ( gg / aa+ga ; or=1.287 , 95%ci : 1.0761.540 ; p=0.006 ) , and recessive model ( aa / ga+gg ; or=0.738 , 95%ci : 0.6290.867 ; p<0.001 ) .
the overall analyses based on all included studies suggested allelic g carriers might have a higher risk for af .
sensitivity analysis was performed to assess the influence of each selected study on the total results .
sensitivity analysis revealed that there was no single study influencing the stability of the crude results , due to no changes in the corresponding pooled ors ( figure 3 ) .
begg s funnel plot showed an approximately symmetrical shape ( figure 4 ) and no publication bias was observed in egger s test ( p= 0.666 ) .
a total of 4 articles [ 5,1719 ] involving the association of cav1 rs3807989 polymorphism with af risk were selected in this meta - analysis , including 3758 af cases and 6126 controls . a detailed flow diagram of the search process for this meta - analysis is displayed in figure 1 .
table 1 shows the main characteristics of the selected studies and the characteristics of included patients are listed in table 2 .
as shown in figure 2 , all 5 comparisons revealed the association between cav1 rs3807989 polymorphism and af risk after meta - analysis with fixed- or random - effects models : allelic model ( g / a ; or=1.228 , 95%ci : 1.0611.420 ; p=0.006 ) , homozygote model ( gg / aa ; or=1.439 , 95%ci : 1.0941.894 ; p=0.009 ) , heterozygote model ( gg / ga ; or=1.257 , 95%ci : 1.0641.486 ; p=0.007 ) , dominant model ( gg / aa+ga ; or=1.287 , 95%ci : 1.0761.540 ; p=0.006 ) , and recessive model ( aa / ga+gg ; or=0.738 , 95%ci : 0.6290.867 ; p<0.001 ) .
the overall analyses based on all included studies suggested allelic g carriers might have a higher risk for af .
sensitivity analysis was performed to assess the influence of each selected study on the total results .
sensitivity analysis revealed that there was no single study influencing the stability of the crude results , due to no changes in the corresponding pooled ors ( figure 3 ) .
begg s funnel plot showed an approximately symmetrical shape ( figure 4 ) and no publication bias was observed in egger s test ( p= 0.666 ) .
we found a significant association of cav1 gene rs3807989 polymorphism with af risk under 5 comparisons : allelic , homozygous , heterozygous , dominant , and recessive genetic models .
these findings suggested that individuals with g allele of cav1 gene rs3807989 polymorphism may experience a higher risk of af .
as the most common clinical sustained arrhythmia with complex pathogenesis , af reportedly has a hereditary susceptibility . in the past few years , numerous case - control and cohort studies
have strongly demonstrated the important roles of multiple genetic variants on genetic predisposition to af .
gwass have identified several susceptibility loci on chromosomes 3p22 , 5q35 , 7q31 , 12p12 , and 12q24 that are potentially associated with af .
three gwass   identified snp rs3807989 in cav1 to be related with af risk in populations of european ancestry . however , several subsequent replication studies yielded inconsistent results ; some studies indicated a significant association of rs3807989 with af , but the others revealed no association .
the snp rs3807989 is located on the chromosome of 7q31 in the second intron of cav1 gene encoding caveolin-1 .
caveolin-1 ( cav1 ) is a key isoform of caveolae , which are 50- to 100-nm plasma membrane vesicles that play roles in cell signaling   and are rich in cholesterol .
moreover , the roles of cav1 in the regulation of plasma lipoprotein metabolism has also been shown .
in addition , af risk is reportedly associated with mutations and genomic variants in genes that encode ion channels .
it was reported that caveolin-1 interacts with potassium channel subunit kir2.1 , generating potassium current ik1 , which affects af development .
furthermore , caveolin-1 was shown to affect transforming growth factor beta 1 ( tgf - b1 ) signaling , which has roles in atrial fibrosis .
therefore , it is possible that snp rs3807989 may enhance risk of af by regulating the function of these cardiac potassium channels and altering tgf - b1 signaling . in this meta - analysis , we pooled all eligible studies to analyze the association between cav1 gene rs3807989 polymorphism and af risk , with a sample size of 3758 af cases and 6126 controls .
firstly , in view of the influence of multiple factors on af , the results would be more precise if individual data were adjusted with some other variables associated with af risk , including coronary heart disease , hypertension , and family history .
secondly , in this meta - analysis we only included the studies published in english , which might have biased the results .
finally , only investigating the cav1 gene rs3807989 polymorphism without considering other genes or polymorphisms might have provided insufficient statistical power ; therefore , further investigation of the interaction of this polymorphism with other risk factors for af is required .
our results revealed a significant association between cav1 gene rs3807989 polymorphism and susceptibility to af , suggesting that the presence of allelic g might be one of the genetic factors conferring susceptibility to af . to confirm this association ,
 backgroundatrial fibrillation ( af ) is the most common sustained arrhythmia affected by multiple cardiovascular risk factors . 
 it is reported that caveolin-1 gene ( cav1 ) rs3807989 polymorphism might be associated with af risk . 
 the goal of this meta - analysis was to confirm the association between cav1 rs3807989 polymorphism and susceptibility to af.material/methodswe carried out a comprehensive literature search through the electronic databases pubmed , medlin , and web of science . 
 we performed a meta - analysis of all selected studies based on cav1 rs3807989 polymorphism genotypes , including 3758 cases and 6126 controls.resultsafter meta - analysis with fixed- or random - effects models , we found significant associations in all 5 comparisons : allelic model ( g / a ; or=1.228 , 95%ci : 1.0611.420 ; p=0.006 ) , homozygote model ( gg / aa ; or=1.439 , 95%ci : 1.0941.894 ; p=0.009 ) , heterozygote model ( gg / ga ; or=1.257 , 95%ci : 1.0641.486 ; p=0.007 ) , dominant model ( gg / aa+ga ; or=1.287 , 95%ci : 1.0761.540 ; p=0.006 ) , and recessive model ( aa / ga+gg ; or=0.738 , 95%ci : 0.6290.867 ; p<0.001 ) . 
 sensitivity analysis results revealed the overall results were robust.conclusionsthe results revealed a significant association between cav1 gene rs3807989 polymorphism and susceptibility to af , suggesting that the presence of allelic g might be one of the genetic factors conferring susceptibility to af . to confirm this association , 
 further well - designed studies are necessary . 