Genetic Polymorphisms of Estrogen Receptors in Patients with Premature Coronary Artery Disease

Background: Estrogen protects against atherosclerosis through its genomic/nongenomic effects. Estrogen receptors (ESR) alpha (1) and beta (2) mediate much estrogen action. Both receptors exist in the arterial wall, but the extent of their distribution in arterial layers is unknown. Allelic variants of the gene encoding ESR1 and ESR2 may alter their expression and function, resulting in genetic variability.

Methods: In the present age-adjusted, case-control study, the prevalence of four mutations in estrogen receptors was analyzed in patients with premature CAD and controls.

Results: Mutation in the ESR1 (PvuII) was more prevalent in the controls (18 vs. 11%; p=0.062) than in CAD patients, and the mutation identified by the XbaI enzyme in the same receptor was associated with reduced apolipoprotein B levels and low body mass index. Mutation of the ESR2 (AluI) was more prevalent in CAD patients (0.6 vs. 18%; p=0.008). Homozygosis for this mutation involved increased body mass index, elevated serum triglycerides and apolipoprotein B, and reduced HDL-cholesterol. Multivariate logistic regression analysis showed dyslipidemia, low serum HDL levels, and ESR2 polymorphism (AluI) [OR=1.89 (95% CI: 1.08-3.34); p=0.034] to be independent risk factors for CAD.

Conclusions: Our data suggest that mutation of the ESR2 is an independent risk marker for premature CAD.