Vargas-Alarcón Gilberto, Pérez-Méndez Óscar, Posadas-Sánchez Rosalinda, González-Pacheco Héctor, Luna-Luna María, Escobedo Galileo, Fragoso José Manuel
Dirección de Investigación, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1 Tlalpan, Mexico City 14080, Mexico.
Departamento de Biología Molecular, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Tlalpan, Mexico City 14080, Mexico.
Biomedicines. 2024 Mar 9;12(3):617. doi: 10.3390/biomedicines12030617.
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 , rs9297994 , rs10504255 , rs8192870 , rs2081687 , rs1457043 and rs10107182 polymorphisms located in the promoter and enhancer regions of the 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 , rs10504255 , rs8192870 , rs2081687 , and rs10107182 were significantly associated with an increased risk of ACS ( < 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 ( < 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 , rs9297944 , rs10504255 , and rs10107182 alleles of the gene, suggesting that such gene variants enhance the development of coronary complications in patients with diabetes ( < 0.05). In summary, our study demonstrated that five polymorphisms situated in the promoter and enhancer regions of the gene are associated with the risk of ACS and higher incidences of dyslipidemia and T2DM in Mexican patients with ACS.
胆固醇7α羟化酶（CYP7A1）是胆汁盐合成中的关键酶，其活性有助于确定胆固醇水平，进而影响患冠状动脉粥样硬化疾病的风险。我们评估了位于该基因启动子和增强子区域的七个（rs3808607、rs9297994、rs10504255、rs8192870、rs2081687、rs1457043和rs10107182）多态性位点，这些位点尚未得到充分研究，是否是墨西哥人群急性冠状动脉综合征（ACS）风险标志物的候选基因。在一组1317例ACS患者和1046例对照受试者中确定了这些多态性。结果表明，在不同的遗传模型下，等位基因rs9297994、rs10504255、rs8192870、rs2081687和rs10107182与ACS风险增加显著相关（P<0.05）。此外，ACS患者中血脂异常的发生率，尤其是高总胆固醇和低密度脂蛋白胆固醇以及低高密度脂蛋白胆固醇血浆水平，在与ACS相关的相同五个风险等位基因携带者中更为常见（P<0.05）。对于该基因rs2081687、rs9297944、rs10504255和rs10107182等位基因纯合的ACS患者中，2型糖尿病（T2DM）的发生率也意外增加，这表明此类基因变异会增强糖尿病患者冠状动脉并发症的发生（P<0.05）。总之，我们的研究表明，位于该基因启动子和增强子区域的五个多态性与墨西哥ACS患者的ACS风险以及血脂异常和T2DM的较高发生率相关。
