Associations of the CYP7A1 Gene Polymorphisms Located in the Promoter and Enhancer Regions with the Risk of Acute Coronary Syndrome, Plasma Cholesterol, and the Incidence of Diabetes

Abstract

Cholesterol-7-alpha hydroxylase (CYP7A1) is a key enzyme in the synthesis of bile salts, and its activity can contribute to determining cholesterol levels and, consequently, the risk of developing coronary atherosclerotic disease. We evaluated whether seven (rs3808607 G/T, rs9297994 G/A, rs10504255 A/G, rs8192870 G/T, rs2081687 C/T, rs1457043 C/T, and rs10107182 C/T) polymorphisms located in the promoter and enhancer regions of the CYP7A1 gene, which have not been sufficiently explored, are candidates of risk markers of acute coronary syndrome (ACS) in the Mexican population. These polymorphisms were determined in a group of 1317 patients with ACS and 1046 control subjects. The results showed that, under different inheritance models, the alleles rs9297994 G, rs10504255 G, rs8192870 T, rs2081687 T, and rs10107182 C were significantly associated with an increased risk of ACS (pC < 0.05). In addition, the incidence of dyslipidemia among patients with ACS, notably high total cholesterol and LDL-cholesterol, and low HDL-cholesterol plasma levels, were more frequent in carriers of the same five risk alleles associated with ACS (p < 0.05). There was also an unexpected increased incidence of type 2 diabetes mellitus (T2DM) in patients with ACS who are homozygous for the rs2081687 T, rs9297944 G, rs10504255 G, and rs10107182 C alleles of the CYP7A1 gene, suggesting that such gene variants enhance the development of coronary complications in patients with diabetes (p < 0.05). In summary, our study demonstrated that five polymorphisms situated in the promoter and enhancer regions of the CYP7A1 gene are associated with the risk of ACS and higher incidences of dyslipidemia and T2DM in Mexican patients with ACS.