Association Between Estrogen Receptor alpha Gene Variation and Cardiovascular Disease.

摘要

Estrogen and related hormones activate estrogen receptors, which in turn regulate genes for some cardiovascular disease (CVD) risk factors. Variants of the estrogen receptor alpha gene (ESR1) have been investigated, in small study populations, in relation to coronary artery disease and variation in levels of high-density lipoprotein (HDL) cholesterol, but little is known about the effects of genetic variation in ESR1 on CVD risk. This prospective study attempted to determine whether the ESR1 c.454-397T>C polymorphism correlates with CVD risk. Participants were 1739 unrelated men and women, ranging in age from 28 to 62 years, from the population-based offspring cohort of the Framingham Heart Study. Total atherosclerotic CVD events (recognized or unrecognized myocardial infarction [MI], angina pectoris, coronary insufficiency, intermittent claudication, death from coronary heart disease, atherothrombotic stroke) were present in 178 individuals followed up from 1971 to 1998. Major atherosclerotic CVD (recognized acute MI, coronary insufficiency, fatal coronary heart disease, atherothrombotic stroke) was found in 83 participants. Fifty-nine persons were recognized as having acute MI. One fifth of those participating in this study were homozygous for the ESR1c.454-397C allele. After adjusting for numerous covariates (age, gender, body mass index, hypertension, diabetes, total and high-density lipoprotein cholesterol, cigarette smoking), the CC genotype correlated significantly with major atherosclerotic CVD (odds ratio, 2.0; 95% confidence interval [CI], 1.3-3.2) compared with the CT or TT genotype. The risk of MI was 3-fold greater in those with the CC genotype (95% CI, 1.7-5.2). Comparable results were obtained when analyzing only men. Total atherosclerotic CVD did not appear to be associated with genotype. This study disclosed an association between a common estrogen receptor genotype, ESR1c.454-397CC, and an increased risk of MI. It seems likely that variations in estrogen receptors could help to explain the apparent effects of combination hormone therapy on the risk of CVD in women.