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

Department of Medicine, Hadassah University Hospital on Mount Scopus (A.R.), Jerusalem, 91240 Israel; Departments of Cardiology (A.P.) and Ophthalmology (A.B.), and Endocrinology and Metabolism Service, Department of Internal Medicine (L.Re., R.D.-P.), Hadassah-Hebrew University Medical Center, Jerusalem, 91120 Israel; Authority for Computation and Information Medical Area Branch, Hebrew University (L.Ro.), Jerusalem, 91120 Israel; and Unit of Epidemiology, Hebrew University-Hadassah School of Public Health (Y.F.), Jerusalem, 91120 Israel

Address all correspondence and requests for reprints to: Rivka Dresner-Pollak, M.D., Endocrinology and Metabolism Service, Hadassah Hebrew-University Medical Center, P.O. Box 12000, Jerusalem, 91120 Israel. E-mail: rivkap{at}md.huji.ac.il.

Context: Sequence variants in the estrogen receptor 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>C and 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.

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