as the most common aneurysm , abdominal aortic aneurysm ( aaa ) mainly occurs in middle - aged or elderly people , and shows an increasing trend worldwide . with the transition of demographic distribution toward an aging society , the incidence of aaa in china is also increasing . although having a benign nature , aaa still has relatively high mortality due to rapid progression and eventual rupture without timely diagnosis and intervention . therefore , understanding the pathogenesis of aaa can greatly benefit screening in high - risk populations for making timely diagnosis and treatment , and thus has become a research focus in recent years . the etiology of aaa involves a complicated process containing a cascade reaction with multiple factors and steps , including genetic / environmental factors and abnormal anatomy , and alternation of hemodynamics and inflammatory response [ 46 ] . among all those risk factors , atp - binding cassette transport protein a1 ( abca1 ) is the most important cell - surface protein facilitating efflux of cholesterol identified to date . it exerts its function mainly through the regulation of reverse cholesterol transport ( rct ) , thus mediating the level of high - density lipoprotein ( hdl ) . in patients with either tangier disease or hdl deficiency , mutations of abca1 gene have been identified , causing deficits of apolipoprotein a - i ( apoa - i ) and hdl , leading to the insufficiency of serum hdl and further atherosclerosis . genetic studies have found the prominent distribution of abca1 mutations in the binding domain and n - terminal region of this gene . in certain atherosclerosis patients , single - nucleotide polymorphism ( snp ) of abca1 gene other studies have also confirmed the correlation between snp of abca1 gene and both atherosclerosis and lipid metabolic disorders . therefore , this study aimed to investigate the correlation between abca1 gene polymorphism of aaa patients and apoa - i and hdl - c , in an attempt to analyze its relationship with aaa pathogenesis . a total of 126 aaa patients ( including 86 males and 40 females , ages 12~89 years , average age=62.312.7 years old ) who were diagnosed and treated in our hospital between january 2012 and december 2014 were recruited in this study . all patients received confirmed diagnosis of aaa via abdominal ultrasound , doppler ultrasound , mscta , or dsa . we recruited 119 healthy volunteers from routine health check - ups in our hospital . among the control group , there were 72 males and 47 females , ages 12~78 years ( average age=61.514.1 years old ) . control group individuals had no atherosclerosis and had normal blood sugar / lipid levels as determined by ultrasound and laboratory tests . any medications that potentially affect lipid metabolism were suspended for 2 weeks before collecting the blood samples . this study was pre - approved by the ethics committee of our hospital and we obtained written consents from all participants or their guardians . fasted venous blood samples ( 10 ml ) were collected within 24 h after admission from elbow vein puncture on all patients . generation information of participants , including age , sex , and body - mass index ( bmi ) , were recorded along with other risk factors , including blood pressure and smoking habits . an automatic biochemical analyzer was used to detect biochemical indexes , including triglyceride ( tg ) , hdl - c , total cholesterol ( tc ) , and low - density lipoprotein ( ldl - c ) by standard enzymatic assays . genomic dna was extracted from peripheral erythrocytes using a whole - blood genomic dna extraction kit ( shanghai shenggong bioengineering technology , china ) following the manual instructions . in brief , 1 after centrifugation at 12 000 rpm for 11min and discarding the supernatant , 0.2 ml solution a ( pbs buffer ) was added in the precipitation for re - suspension , followed by the addition of 20 l rnase a ( 10 mg / ml ) . the mixture was then incubated at room temperature for 10 min , followed by the addition of 20 l proteinase k ( 10 mg / ml ) . the sample was then resolved by 65c water bath and loaded onto the absorbent column , which was centrifuged and eluted by elution buffer . the pcr reaction mixture included specific primers ( 0.1 m ; forward , 5-gtatt tttgc aaggc tacca gttac atttg acaa-3 ; reverse , 5-gattg gcttc aggat gtcca tgttg gaa-3 ; designed as previously documented   and synthesized by shanghai shenggong bioengineering technology , china ) , 0.5 g of genomic dna , 0.25 mm dntps , tag polymerase , 2 mm mgcl2 and 10x tag buffer ( invitrogen , us ) . the amplification parameters were : 94c per - denature for 5 min , followed by 30 cycles each consisting of 94c denature for 1 min , 58c annealing for 50 s and 72c elongation for 25 s. the reaction ended with 72c elongation for another 10 min . pcr products ( 10 l ) were digested by 2 l restriction enzyme ( takara , china ) at 37c for 6 h. the digestion products were further amplified and sequenced by shanghai shenggong bioengineering technology , china . distribution of alleles and genotypes at loci rs2230806 ( r219k ) of abca1 gene was determined by sequencing . spss 20.0 software package was used to analyze all collected data , of which enumeration data , including genotype and allele frequencies , were analyzed by chi - square test . the homogeneity of the sample was further evaluated by hardy - weinberg ( h - w ) equilibrium . one - way analysis of variance ( anova ) was used to compare means among multiple groups . the correlation between genotype / allele frequency and occurrence of aaa a total of 126 aaa patients ( including 86 males and 40 females , ages 12~89 years , average age=62.312.7 years old ) who were diagnosed and treated in our hospital between january 2012 and december 2014 were recruited in this study . all patients received confirmed diagnosis of aaa via abdominal ultrasound , doppler ultrasound , mscta , or dsa . we recruited 119 healthy volunteers from routine health check - ups in our hospital . among the control group , there were 72 males and 47 females , ages 12~78 years ( average age=61.514.1 years old ) . control group individuals had no atherosclerosis and had normal blood sugar / lipid levels as determined by ultrasound and laboratory tests . any medications that potentially affect lipid metabolism were suspended for 2 weeks before collecting the blood samples . this study was pre - approved by the ethics committee of our hospital and we obtained written consents from all participants or their guardians . fasted venous blood samples ( 10 ml ) were collected within 24 h after admission from elbow vein puncture on all patients . generation information of participants , including age , sex , and body - mass index ( bmi ) , were recorded along with other risk factors , including blood pressure and smoking habits . an automatic biochemical analyzer was used to detect biochemical indexes , including triglyceride ( tg ) , hdl - c , total cholesterol ( tc ) , and low - density lipoprotein ( ldl - c ) by standard enzymatic assays . genomic dna was extracted from peripheral erythrocytes using a whole - blood genomic dna extraction kit ( shanghai shenggong bioengineering technology , china ) following the manual instructions . in brief , 1 after centrifugation at 12 000 rpm for 11min and discarding the supernatant , 0.2 ml solution a ( pbs buffer ) was added in the precipitation for re - suspension , followed by the addition of 20 l rnase a ( 10 mg / ml ) . the mixture was then incubated at room temperature for 10 min , followed by the addition of 20 l proteinase k ( 10 mg / ml ) . the sample was then resolved by 65c water bath and loaded onto the absorbent column , which was centrifuged and eluted by elution buffer . the pcr reaction mixture included specific primers ( 0.1 m ; forward , 5-gtatt tttgc aaggc tacca gttac atttg acaa-3 ; reverse , 5-gattg gcttc aggat gtcca tgttg gaa-3 ; designed as previously documented   and synthesized by shanghai shenggong bioengineering technology , china ) , 0.5 g of genomic dna , 0.25 mm dntps , tag polymerase , 2 mm mgcl2 and 10x tag buffer ( invitrogen , us ) . the amplification parameters were : 94c per - denature for 5 min , followed by 30 cycles each consisting of 94c denature for 1 min , 58c annealing for 50 s and 72c elongation for 25 s. the reaction ended with 72c elongation for another 10 min . pcr products ( 10 l ) were digested by 2 l restriction enzyme ( takara , china ) at 37c for 6 h. the digestion products were further amplified and sequenced by shanghai shenggong bioengineering technology , china . distribution of alleles and genotypes at loci rs2230806 ( r219k ) of abca1 gene was determined by sequencing . spss 20.0 software package was used to analyze all collected data , of which enumeration data , including genotype and allele frequencies , were analyzed by chi - square test . the homogeneity of the sample was further evaluated by hardy - weinberg ( h - w ) equilibrium . one - way analysis of variance ( anova ) was used to compare means among multiple groups . the correlation between genotype / allele frequency and occurrence of aaa we compared general information , including age , sex , smoking history , diabetes , and hypertension , between disease and control groups . no statistically significant difference regarding sex or age results ( table 1 ) showed significantly higher incidence of hypertension in aaa patients compared to the control group . the male - to - female ratio of aaa incidence was 2.15-fold higher ( p<0.05 ) . other indexes , including bmi , smoking , diabetes , and fasted blood glucose ( fbg ) level , showed no significant difference between the 2 groups ( p>0.05 ) . as shown in table 2 , aaa patients had significantly higher tg and ldl - c levels compared to those in the control group , along with lower hdl - c and apoa - i levels ( p<0.05 in all cases ) . the distribution of genotypes in both groups fit hardy - weinberg equilibrium , suggesting the homogeneity of both populations . in a comparison of polymorphisms at loci rs2230806 ( r219k ) of abca1 gene , the frequency of kk and rr genotypes was significantly different between the disease and control groups ( table 3 , p<0.05 ) . . a further analysis of allele frequency showed significantly lower incidence of r allele in the disease group compared to the control group ( p<0.05 ) . a further analysis of the correlation between abca1 genotype and blood lipid level showed significantly higher apoa - i and hdl - c levels in aaa patients carrying r alleles ( both rr and rk genotypes at r219k loci ) . the level of tc , tg , and ldl - c , however , showed no statistically significant difference between the 2 groups ( table 4 , p>0.05 ) . logistic regression analysis was used to analyze the correlation between abca1 genotypes and the occurrence of aaa . as shown in table 5 , no significant correlation was discovered between kk genotype and aaa occurrence . rr genotype , however , was correlated with aaa occurrence ( or=0.45 , p<0.05 ) , as was rk genotype ( or=0.56 , p<0.05 ) . the r allele , therefore was correlated with aaa pathogenesis ( or=0.66 , p<0.05 ) . we compared general information , including age , sex , smoking history , diabetes , and hypertension , between disease and control groups . no statistically significant difference regarding sex or age results ( table 1 ) showed significantly higher incidence of hypertension in aaa patients compared to the control group . the male - to - female ratio of aaa incidence was 2.15-fold higher ( p<0.05 ) . other indexes , including bmi , smoking , diabetes , and fasted blood glucose ( fbg ) level , showed no significant difference between the 2 groups ( p>0.05 ) . as shown in table 2 , aaa patients had significantly higher tg and ldl - c levels compared to those in the control group , along with lower hdl - c and apoa - i levels ( p<0.05 in all cases ) . the distribution of genotypes in both groups fit hardy - weinberg equilibrium , suggesting the homogeneity of both populations . in a comparison of polymorphisms at loci rs2230806 ( r219k ) of abca1 gene , the frequency of kk and rr genotypes was significantly different between the disease and control groups ( table 3 , p<0.05 ) . . a further analysis of allele frequency showed significantly lower incidence of r allele in the disease group compared to the control group ( p<0.05 ) . a further analysis of the correlation between abca1 genotype and blood lipid level showed significantly higher apoa - i and hdl - c levels in aaa patients carrying r alleles ( both rr and rk genotypes at r219k loci ) . the level of tc , tg , and ldl - c , however , showed no statistically significant difference between the 2 groups ( table 4 , p>0.05 ) . logistic regression analysis was used to analyze the correlation between abca1 genotypes and the occurrence of aaa . as shown in table 5 , no significant correlation was discovered between kk genotype and aaa occurrence . rr genotype , however , was correlated with aaa occurrence ( or=0.45 , p<0.05 ) , as was rk genotype ( or=0.56 , p<0.05 ) . the r allele , therefore was correlated with aaa pathogenesis ( or=0.66 , p<0.05 ) . as one of the most common dilated vascular diseases , aaa can be classified as symptomatic and asymptomatic sub - types . the former has relatively high diagnostic rate and treatment efficacy , but the asymptomatic aaa presents an insidious disease onset , impeding timely treatment and causing a higher mortality rate after aneurysm rupture and hemorrhagic shock . therefore , both etiology and treatment of aaa are now receiving considerable research interest . under influences from various predisposing factors , aaa may weaken the basal layer of the aortic wall , causing elevated degradation and decreased synthesis of elastin . the hemodynamic force further expands the aneurysm , aggravating the disease condition due to atherosclerosis and vascular dilation . in previous studies , the present study revealed the male - biased occurrence of aaa , which is consistent with previous reports . a significantly higher percentage of hypertension existed in the disease group when compared to the control group , suggesting the relationship between hypertensive atherosclerosis and aaa occurrence . other studies reported smoking , obesity , and abnormal blood glucose as factors affecting aaa . this study , however , did not find any significant difference regarding bmi , smoking , or diabetes between aaa patients and control individuals . abnormal blood lipid level usually induces atherosclerosis , which further facilitates the occurrence of aaa . this study found significantly elevated blood tg and ldl - c in aaa patients , as well as lower hdl - c and apoa - i levels . as the most important gene regulating human lipid metabolism , abca1 gene locates at 9q31 region and contains more than 50 exons plus 49 introns , making the total length of the gene over 150 kb . the promoter region , which is localized 1453 bp upstream of the start codon , has multiple binding sites for transcriptional factors involved in lipid metabolism regulation . abca1 gene has been suggested to be related with atherosclerosis and lipid metabolic disorders , both of which contribute to the occurrence and progression of aaa . the snp pattern of abca1 has been reported , especially at r219k loci , which locates at 1051 nt of 7 exon , which has significant relationship with various diseases , including hyperlipidemia , coronary heart disease , and atherosclerosis , further suggesting the important role of abca1 gene polymorphism in aaa . this study revealed a statistically significant difference in frequency of kk and rr genotypes between aaa patients and the control group , as supported by lower incidence of rr genotype and r alleles in the disease group . further correlation analysis showed higher apoa - i and hdl - c levels in r allele carriers within aaa patients compared to non - carrier patients . moreover , both rr / rk genotypes and r allele were closely correlated with aaa pathogenesis . this study for the first time demonstrates the close relationship between r219k polymorphism of abca1 gene and occurrence of aaa ; r allele at this locus may regulate the pathogenesis and progression of aaa . therefore , further studies are needed on the detailed mechanism of r219k mutation - induced blood lipid abnormalities . such studies are expected to provide evidence useful for developing large - scale screening , early diagnosis and treatment of aaa .