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The influence of Estrogen Receptor 1 (ESR1) gene -397T&gt;C (PvuII) and -351A&gt;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&gt;C and -351A&gt;G gene polymorphisms were significantly higher in CAD patients than control subjects ( p  &lt; 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&gt;C polymorphism, the ERα mRNA expression was highest in CAD patients with wild type homozygous TT genotype (2 -∆ct  = 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 -∆ct  = 0.09), and intermediate expression level in heterozygous TC genotype (2 -∆ct  = 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&gt;C and -351A&gt;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&gt;C polymorphism with consequent increased CAD susceptibility.

indian journal of clinical biochemistry

Clinical Importance of Estrogen Receptor 1 (ESR1) Gene Polymorphisms and Their Expression Patterns in Coronary Artery Disease Patients: A Study from India