Polymorphisms and Haplotypes of the Estrogen Receptor-[Beta] Gene (ESR2) and Cardiovascular Disease in Men and Women (Molecular Diagnostic and Genetics‪)‬

The development of atherothrombotic cardiovascular disease (CVD) [5] is likely polygenic. The cardiovascular effects of estrogen are mediated through binding to specific estrogen receptors at the cytosolic and nuclear level. Two separate estrogen receptors have been identified: estrogen receptor-[alpha] (ER-[alpha]) and estrogen receptor-[beta] (ER-[beta]). Although polymorphisms of the ER-[alpha] gene (ESR1) [6] have recently received attention as possible contributors to CVD risk in men and women (1-8), the relationship between genetic variation of the ER-[beta] gene (ESR2) and CVD has not been as well studied. Several lines of evidence support a potential role of ESR2 in CVD. ER-[beta] is highly expressed in endothelial and vascular smooth muscle cells (9). ER-0 has been associated with coronary plaque (9). In autopsy studies, ER-[beta] expression positively correlates with increased coronary artery plaque area in both women and men (10, 11). Polymorphisms of ESR2 have been associated with left ventricular mass and left ventricular wall thickness in women but not men (12). To the best of our knowledge, only one published study has evaluated ESR2 and atherosclerosis. In a Brazilian case control study, an ESR2 variant (rs4986938) was more common among cases with premature coronary artery disease than among controls (13).