A functional polymorphism in the CYP3A4 gene is associated with increased risk of coronary heart disease in the Chinese Han population.

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 CYP3A41G (rs2242480), has been identified. The aim of this study was to evaluate the potential relationship between the CYP3A41G 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 CYP3A41G. We also analysed the functional significance of IVS10+12G>A using the dual-luciferase reporter assay. The results showed that the frequency of the CYP3A41G allele was 0.290 and the CYP3A4*1G/1G genotype was 0.090 in the patients with CHD. The patients with the CYP3A41G/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 CYP3A41G/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 CYP3A41G contributes to the susceptibility of CHD in the Chinese Han population, which may be useful for the study of specific molecular pathogenesis for CHD.