Abstract 12977: Plasma Estradiol Levels, Estrogen Receptor Polymorphisms and Ischemic Arterial Disease in Postmenopausal Women: The Three-city Prospective Cohort Study
Background: High levels of endogenous estrogen have been related to adverse health outcomes, including ischemic arterial disease (IAD), in older postmenopausal women. Whether estrogen receptor polymorphisms modulate the effects of estradiol on IAD has not been investigated.
Methods: In the Three-City prospective cohort study of subjects over 65 years, we designed a case-cohort study in which plasma levels of total 17β-estradiol were measured. After exclusion of postmenopausal women using hormone therapy, a subcohort of 533 subjects and 105 incident cases of first IAD events were analyzed. Polymorphisms of estrogen receptor alpha (rs2234693 and rs9340799) and beta (rs1256049, rs4986938 and rs1271572) were genotyped.Using weighted Cox proportional-hazards models, hazard ratios (HRs) for IAD risk were estimated in relation to 1-standard deviation increase of estradiol level by genotypes.
Results: Neither estradiol levels nor IAD risk were significantly associated with estrogen receptor polymorphisms. Estradiol levels were positively related to IAD risk in women with rs9340799 AA genotype but not in women with AG/GG genotype (HR: 1.62, 95% CI: 1.22-2.17, p≤0.01 and HR: 1.03, 95% CI: 0.81-1.30, p=0.84, respectively; p for interaction =0.01). Similar significant interaction was observed for the risk of coronary heart disease, but not for stroke risk. A borderline significant interaction was found for rs2234693, showing an increased risk of coronary heart disease with estradiol levels in women with TT genotype versus TC/CC.
Conclusion: Genetic variations of rs9340799 in estrogen receptor alpha may modulate the risk of IAD related to high endogenous estradiol levels in older postmenopausal women.
- © 2013 by American Heart Association, Inc.