Polymorphisms and haplotypes of the estrogen receptor-β gene (ESR2) and cardiovascular disease in men and women
Polymorphisms and haplotypes of the estrogen receptor-β gene (ESR2) and cardiovascular disease in men and women
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DOI：
10.1373/clinchem.2007.091454
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发表时间：
2007-10-01
影响因子：
9.3
通讯作者：
Zee, Robert Y. L.
中科院分区：
文献类型：
--
作者：
Rexrode, Kathryn M.;Ridker, Paul M.;Zee, Robert Y. L.
背景：队列研究表明雌激素受体-1基因（ESRI）变异与心血管疾病（CVD）之间存在关联，但缺乏雌激素受体-13基因（ESR2）变异的影响数据。方法：对来自女性健康研究的296名白人女性和来自医师健康研究的566名患有CVD（心肌梗死NO或缺血性卒中）的白人男性进行ESR2基因的三种多态性及其相关单倍型的评估，每一种多态性与队列研究中没有CVD的成员1:1匹配。在基线时收集血液样本和心血管风险信息。结果：发生心血管疾病或心肌梗死但未发生缺血性卒中的女性，而非男性，更容易携带rs1271572多态性变异T等位基因（P = 0.05和0.02），而较少携带rs1256049多态性变异A等位基因（P = 0.003和0.004）。rs4986938无关联。在条件logistic多变量回归中，rs1271572变异与CVD（比值比(OR) = 1.49,95% CI: 1.10-2.01）和心肌梗死（OR = 1.46,95% Cl: 0.96-2.23）的几率增加相关，而rs1256049变异与女性CVD （OR = 0.37, 95% CI: 0.17-0.79）和心肌梗死（OR = 0.25, 95% CI: 0.09-0.73）的几率降低相关。包含rs1271572变异的普通单倍型与女性心肌梗死风险增加7倍相关。结论：ESR2两种紧密相关的多态性与心血管疾病（尤其是心肌梗死）的风险相关，但与男性无关。ESR2基因变异和心血管疾病风险的进一步研究是有必要的。(C) 2007年美国临床化学学会。
Background: Cohort studies suggest an association between variation in the estrogen receptor-a gene (ESRI) and cardiovascular disease (CVD), but data are lacking for the effect of variation in the estrogen receptor-13 gene (ESR2).Methods: Three polymorphisms of the ESR2 gene, and their associated haplotypes, were evaluated in 296 white women from the Women's Health Study and 566 white men from the Physicians' Health Study who developed CVD [myocardial infarction NO or ischemic stroke], each matched 1:1 to a member of the cohort study who remained free from CVD. Blood samples and cardiovascular risk information were collected at baseline.Results: Women, but not men, who developed CVD or MI, but not ischemic stroke, were more likely to have the rs1271572 polymorphism variant T allele (P = 0.05 and 0.02) and less likely to have the rs1256049 polymorphism variant A allele (P = 0.003 and 0.004). No associations were observed for rs4986938. In conditional logistic multivariate regression, the rs1271572 variant was associated with increased odds of CVD [odds ratio (OR) = 1.49,95% CI: 1.10-2.01]and MI (OR = 1.46,95% Cl: 0.96-2.23), whereas the rs1256049 variant was associated with decreased odds of CVD (OR = 0.37, 95% CI: 0.17-0.79) and MI (OR = 0.25, 95% CI: 0.09-0.73) in women. A common haplotype that included the rs1271572 variant was associated with a 7-fold increased risk of MI in women.Conclusions: Two tightly linked polyrnorphisms of ESR2 were associated with risk of CVD, particularly MI, in women but not men. Additional studies of ESR2 genetic variation and risk of CVD are warranted. (C) 2007 American Association for Clinical Chemistry.