title: A functional polymorphism in the CYP3A4 gene is associated with increased risk of coronary heart disease in the Chinese Han population.
abstract: CYP3A4 is a major member of the cytochrome P450 (CYP) enzymes which play crucial roles in cardiovascular diseases. Recently, a novel polymorphism in the CYP3A4 gene, IVS10+12G>A, named CYP3A4*1G (rs2242480), has been identified. The aim of this study was to evaluate the potential relationship between the CYP3A4*1G allele and the susceptibility of coronary heart disease (CHD). A total of 628 individuals (322 unrelated patients with CHD and 306 age- and sex-matched healthy controls) were investigated in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to identify CYP3A4*1G. We also analysed the functional significance of IVS10+12G>A using the dual-luciferase reporter assay. The results showed that the frequency of the CYP3A4*1G allele was 0.290 and the CYP3A4*1G/*1G genotype was 0.090 in the patients with CHD. The patients with the CYP3A4*1G/*1G genotype had higher CHD risk, with an odds ratio (OR) of 3.84 (p=0.025; 95% CI=1.32-12.65) after adjustment for conventional risk factors. A gender-dependent difference was also observed. The CYP3A4*1G/*1G frequency was significantly higher in female patients than in the controls (p=0.034, OR=3.02, 95% CI=1.04-8.70). Furthermore, the dual-luciferase reporter assay indicated that the A allele at IVS10+12G>A had a significantly higher transcriptional activity than the G allele. Our results imply that CYP3A4*1G contributes to the susceptibility of CHD in the Chinese Han population, which may be useful for the study of specific molecular pathogenesis for CHD.
authors.affiliation: Guangzhou General Hospital of Guangzhou Military Command, 111 Liuhua Road, Guangzhou, Guangdong, China.
authors.forename: Bao-xia
authors.initials: BX
authors.lastname: He
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Jian
authors.initials: J
authors.lastname: Qiu
authors.forename: Liang
authors.initials: L
authors.lastname: Tao
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
authors.forename: Shu-jin
authors.initials: SJ
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D054458:Amplified Fragment Length Polymorphism Analysis; D044466:Asian People / Q000235:genetics; D002681:China; D003327:Coronary Disease / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005787:Gene Frequency; D017930:Genes, Reporter; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D056945:Hep G2 Cells; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012727:Sex Characteristics
chemical_list: D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human