Estrogen Receptor Gene Polymorphisms Are Associated with the Angiographic Extent of Coronary Artery Disease

Context: Sequence variants in the estrogen receptor α gene (ESR1) may alter the atheroprotective effects of estrogens, and be associated with the severity of coronary artery disease (CAD). Objective: This study seeks to investigate the association between the ESR1 haplotype created by the c.454-397 T>Cand c.454-351 A>G polymorphisms, the length of the (TA)_n repeats, and the angiographic extent of CAD. Design: Consecutive subjects with age younger than or equal to 55 yr who had undergone coronary angiography between November 2003 and January 2004 were included in the study. Setting: The study was conducted in a referral center. Patients: One hundred five subjects with age younger than or equal to 55 yr (87 males, 18 females) participated in the study. Main Outcome Measures: The angiographic extent of CAD was graded by number of: 1) major coronary vessels with more than 50% narrowing (NMCV); 2) narrowed major coronary vessels and/or their second-order branch (NCV); and 3) coronary segments with any narrowing (NN). Analysis of covariance was used to test the effect of haplotype and (TA)_n length on the angiographic extent of CAD with gender and number of CAD risk factors (hyperlipidemia, diabetes, hypertension, obesity, smoking, and family history of CAD) as covariates. Results: The ESR1 haplotype c.454-397C and c.454-351G was associated with NCV and NN (P = 0.008 and 0.02, respectively). Carriers of two copies of haplotype C-G had a higher number of NCV compared with subjects with one or no copies combined (3.5 ± 2.2 vs. 2.3 ± 1.9, P = 0.012, respectively). A longer (TA)_n repeat was associated with NCV (P = 0.04). Conclusions: The ESR1 c.454-397C and c.454-351G haplotype and longer (TA)_n repeats are associated with the extent of CAD in young subjects, independent of the known CAD risk factors.