Estrogen receptor alpha gene polymorphisms are associated with the angiographic extent of coronary artery disease

J Clin Endocrinol Metab. 2005 Dec;90(12):6556-60. doi: 10.1210/jc.2005-0236. Epub 2005 Sep 13.

Abstract

Context: Sequence variants in the estrogen receptor alpha 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Coronary Angiography*
  • Coronary Artery Disease / diagnostic imaging*
  • Coronary Artery Disease / genetics*
  • Estrogen Receptor alpha / genetics*
  • Female
  • Gene Dosage
  • Gene Frequency
  • Haplotypes
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*

Substances

  • Estrogen Receptor alpha