Association of polymorphisms in the sex hormone genes with the presence and severity of coronary artery disease.

Objective: Coronary artery disease (CAD) is an important public health problem worldwide. Therefore, it is important to identify the molecular mechanisms and the candidate gene polymorphisms involved in the development of CAD. In this study, we focused on 2 polymorphisms of the atherosclerosis-related genes, ESR1 and CYP19A1.

Methods: Unselected 339 individuals who underwent coronary angiography were divided into 2 groups: those with normal coronary arteries (≤30% stenosis) and those with critical disease (≥50% stenosis). Individuals were genotyped for CYP19A1 rs10046 C/T and ESR1 rs2175898 A/G polymorphisms using hybridization probes in real-time PCR. In addition, Gensini and SYNTAX scores were assessed.

Results: ESR1 polymorphism was significantly associated with CAD in men (p=0.036) via G allele carriage. Multiple logistic regression analyses showed that ESR1 rare allele carriage was associated with CAD presence (Odds ratio=2.12, 95% confidence interval 1.01-4.1, p=0.025), adjusted for age, HDL-C, LDL-C and smoking status in the male group. CYP19A1 rs10046 T allele carriers had a 2.84-fold increased risk for complex CAD in multiple logistic regression analysis (p=0.016). Furthermore, the univariate analysis of variance indicated that T allele carriage of rs10046 polymorphism was associated with increased SYNTAX and Gensini scores (p<0.05). Female patients who were ESR1 G allele carriers with CAD had higher adiponectin levels (p=0.005), whereas HbA1c levels were associated with T allele of CYP19A1 in the CAD group (p=0.004) and male CAD group (p=0.018).

Conclusion: The CYP19A1 and ESR1 polymorphisms were associated with the presence and severity of CAD. These gene polymorphisms warrant further studies for the elucidation of their contribution to CAD development.