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Submitted on February 4, 2005
Accepted on September 6, 2005
Department of Medicine, Hadassah University Hospital on Mount Scopus, Departments of Cardiologyand Ophthalmology, Hadassah-Hebrew University Medical Center, Authority for Computation and Information Medical Area Branch, Hebrew University, Unit of Epidemiology, Hebrew University-Hadassah School of Public Health, and the Endocrinology and Metabolism Service, Department of Internal Medicine, Hadassah-Hebrew University Medical center, Jerusalem, Israel
* To whom correspondence should be addressed. 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- To investigate the association between the ESR1 haplotype created by the c.454-397T>C and c.454-351A>G polymorphisms, the length of the (TA)n repeats and the angiographic extent of CAD.
Design- Consecutive subjects with age 
55 yr who had undergone coronary angiography between November 2003 and January 2004 were included.
Setting- Referral center.
Patients- One hundred and five subjects with age 55 yr (87 males, 18 females).
Main Outcome Measures- The angiographic extent of CAD was graded by number of: 1) Major coronary vessels with >50% narrowing (NMCV). 2) Narrowed major coronary vessels and/or their second-order branch (NCV). 3) Coronary segments with any narrowing (NN). ANCOVA 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 2 copies of haplotype C-G had a higher number of NCV compared with subjects with 1 or 0 copies combined (3.5 ± 2.2 vs. 2.3 ± 1.9, P = 0.012, respectively). A longer (TA)n repeats 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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