Abstract
BackgroundThe cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) gene is expressed in the vascular endothelium, which metabolizes arachidonic acid into 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs). 20-HETE mediates cardiovascular homeostasis and growth response in vascular smooth muscle cells (VSMCs) as well as the anti-platelet effect. EETs are potent endogenous vasodilators and inhibitors of vascular inflammation. This study assessed the association between human CYP1A1 gene polymorphisms and coronary artery disease (CAD) in the Uygur and Han in China.MethodsTwo independent case–control studies that recruited Han (389 patients with CAD and 411 controls) and Uygur participants (293 patients with CAD and 408 controls) analyzed the relationship between CYP1A1 single nucleotide polymorphisms (SNPs: rs4886605, rs12441817, rs4646422 and rs1048943) and CAD. All patients with CAD and controls were genotyped for the four SNPs of CYP1A1 using TaqMan SNP genotyping assays.ResultsIn the Uygur group, the distribution of the dominant model(CC vs CT + TT) of rs4886605 for the total sample and the males was significantly different between CAD patients and control participants (P = 0.001 and P = 0.012, respectively), The difference remained significant after a multivariate adjustment (P = 0.018, P = 0.015, respectively). The rs12441817 was also associated with CAD in a dominant model for all participants (P = 0.003) and men (P = 0.012), and the difference remained significant after a multivariate adjustment (P = 0.016, P = 0.002, respectively). However, we did not observe differences in the Uygur females and Han group with regard to the allele frequency or genotypic distribution of rs4886605 and rs12441817 between patients with CAD and control participants. Patients with CAD did not significantly differ from the control participants with regard to the distributions of rs4646422 and rs1048943 genotypes, the dominant model, the recessive model, or allele frequency in the Han and Uygur groups.ConclusionBoth rs4886605 and rs12441817 SNPs of the CYP1A1 gene are associated with CAD in the Uygur population of China.
Highlights
Coronary artery disease (CAD) accounts for nearly 40% of all the Causes of mortality in developed countries [1,2]
In addition to the roles that CYP1A1 plays in metabolizing exogenous compounds such as polycyclic aromatic hydrocarbons (PAHs) and aromatic amines that increase the development of atherosclerotic lesions, it can metabolize arachidonic acid to terminal 20-hydroxyeicosatetraenoic acid (20-HETEs; 75–90%) and, to a lesser extent, epoxyeicosatrienoic acids (EETs; 5–7%) [17,18,19]. 20-HETE plays critical roles in the regulation of cardiovascular, renal and pulmonary homeostasis as well as the growth response in vascular smooth muscle cells (VSMCs), cardiac function and vascular tone [7]
BMI was significantly higher among total, men and women patients with coronary artery disease (CAD) than their control counterparts in Uygur populations, and the plasma concentration of total cholesterol (TC) was significantly higher for women group
Summary
Two independent case–control studies that recruited Han (389 patients with CAD and 411 controls) and Uygur participants (293 patients with CAD and 408 controls) analyzed the relationship between CYP1A1 single nucleotide polymorphisms (SNPs: rs4886605, rs12441817, rs4646422 and rs1048943) and CAD. All patients with CAD and controls were genotyped for the four SNPs of CYP1A1 using TaqMan SNP genotyping assays
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