Sumi Mamta P, Guru Sameer Ahmad, Mir Rashid, Masroor Mirza, Bhat Musadiq A, Girish M P, Saxena Alpana
1Department of Biochemistry, Maulana Azad Medical College, University of Delhi, New Delhi, India.
2Department of Cardiology, GB Pant Hospital, University of Delhi, New Delhi, India.
Indian J Clin Biochem. 2019 Apr;34(2):133-142. doi: 10.1007/s12291-019-00827-y. Epub 2019 Apr 5.
The influence of Estrogen Receptor 1 (ESR1) gene -397T>C (PvuII) and -351A>G (XbaI) polymorphisms on the risk of development of coronary artery disease (CAD) in the north Indian population was analysed. We hypothesized that ESR1 gene polymorphisms may influence the susceptibility to CAD through variation in Estrogen Receptor α (ERα) expression. To assess this concept, we evaluated ERα mRNA expression in blood plasma of CAD patients. The study included hundred CAD patients who showed presence of greater than 50% luminal stenosis in at least one major coronary artery in angiography along with hundred age and sex matched healthy controls. The ESR1 polymorphisms were investigated by PCR-RFLP. Quantitative Real Time PCR was carried out for the measurement of ERα mRNA expression. The results showed that genotypic frequencies of ESR1 -397T>C and -351A>G gene polymorphisms were significantly higher in CAD patients than control subjects ( < 0.0001). A significantly increased CAD risk was also found in dominant and codominant inheritance model for both of the SNPs. In gender based analysis these findings were replicated only in male subgroup. In case of -397T>C polymorphism, the ERα mRNA expression was highest in CAD patients with wild type homozygous TT genotype (2 = 0.28). A mutant 'C' allele, dose dependent, significant decrease in trend in ERα mRNA expression was observed, with lowest expression in mutant homozygous CC genotype (2 = 0.09), and intermediate expression level in heterozygous TC genotype (2 = 0.14) subgroups of CAD patients. In conclusion, this study demonstrates a significantly heightened risk of CAD associated with the inheritance of mutant genotypes of ESR1 -397T>C and -351A>G gene polymorphisms, in the north Indian population. This is the first report of a lowered ERα mRNA expression in conjunction with the presence of mutant 'C' allele of ESR1 -397T>C polymorphism with consequent increased CAD susceptibility.
分析了雌激素受体1（ESR1）基因-397T>C（PvuII）和-351A>G（XbaI）多态性对印度北部人群冠状动脉疾病（CAD）发生风险的影响。我们假设ESR1基因多态性可能通过雌激素受体α（ERα）表达的变化影响CAD易感性。为评估这一概念，我们检测了CAD患者血浆中ERα mRNA的表达。该研究纳入了100例CAD患者，这些患者在血管造影中至少有一支主要冠状动脉管腔狭窄超过50%，同时纳入了100例年龄和性别匹配的健康对照。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测ESR1多态性。采用定量实时PCR检测ERα mRNA表达。结果显示，CAD患者中ESR1 -397T>C和-351A>G基因多态性的基因型频率显著高于对照组（<0.0001）。在两个单核苷酸多态性（SNP）的显性和共显性遗传模型中也发现CAD风险显著增加。在基于性别的分析中，这些发现仅在男性亚组中得到重复。对于-397T>C多态性，野生型纯合子TT基因型的CAD患者中ERα mRNA表达最高（2 = 0.28）。观察到突变的“C”等位基因呈剂量依赖性，导致ERα mRNA表达呈显著下降趋势，突变纯合子CC基因型表达最低（2 = 0.09），CAD患者杂合子TC基因型亚组表达水平居中（2 = 0.14）。总之，本研究表明，在印度北部人群中，ESR1 -397T>C和-351A>G基因多态性的突变基因型遗传与CAD风险显著升高相关。这是首次报道ESR1 -397T>C多态性的突变“C”等位基因与ERα mRNA表达降低以及CAD易感性增加有关。
