Post-genomic update on a classical candidate gene for coronary artery disease: ESR1.
Post-genomic update on a classical candidate gene for coronary artery disease: ESR1.
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冠状动脉疾病经典候选基因的后基因组更新：ESR1。
DOI：
10.1161/circgenetics.111.960583
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发表时间：
2011
期刊：
影响因子：
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通讯作者：
CARDIoGRAMConsortium
中科院分区：
文献类型：
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作者：
Lucas,Gavin;Lluís-Ganella,Carla;Subirana,Isaac;Sentí,Mariano;Willenborg,Christina;Musameh,MuntaserD;Schwartz,StephenM;O'Donnell,ChristopherJ;Melander,Olle;Salomaa,Veikko;Elosua,Roberto;CARDIoGRAMConsortium
研究背景除年龄外，性别是冠心病最重要的危险因素。保护女性免受CAD的机制在很大程度上仍然未知，但观察到的性别差异表明生殖类固醇激素信号系统的参与。基因编码的雌激素受体α（ESR1）的遗传关联研究显示出相互矛盾的结果，虽然只有有限的范围内的基因变异已经investigated.Methods和ResultsWe利用先进的新方法和复杂的疾病遗传学资源提供的信息，重新审视的问题ofESR1的作用，CAD的风险。我们对14项全基因组关联研究进行了荟萃分析（心脏病发现分析，N= 187000），以寻找CAD风险与ESR1编码区、非编码区和侧翼区常见遗传变异之间的人群范围和性别特异性关联。除了来自MIGen（N= 6000）、WTCCC（N= 7400）和Fragrance（N= 3700）研究的样本外，我们还通过使用来自1000个基因组计划的数据构建的一组单倍型进行插补，将该搜索扩展到大量常见和罕见变异。尽管ERα在血管组织中的广泛表达，我们发现没有证据表明参与的共同或低频率的遗传变异在整个theESR1基因在修改CAD的风险，无论是在一般人群中或作为一个函数sexual.ConclusionsWe建议，未来的研究在CAD风险的性别相关差异的遗传基础上，首先应优先考虑其他基因在生殖类固醇激素生物合成系统。
BackgroundAfter age, sex is the most important risk factor for coronary artery disease (CAD). The mechanism through which women are protected from CAD is still largely unknown, but the observed sex difference suggests the involvement of the reproductive steroid hormone signaling system. Genetic association studies of the gene-encoding Estrogen Receptor α (ESR1) have shown conflicting results, although only a limited range of variation in the gene has been investigated.Methods and ResultsWe exploited information made available by advanced new methods and resources in complex disease genetics to revisit the question ofESR1's role in risk of CAD. We performed a meta-analysis of 14 genome-wide association studies (CARDIoGRAM discovery analysis, N=≈87 000) to search for population-wide and sex-specific associations between CAD risk and common genetic variants throughout the coding, noncoding, and flanking regions ofESR1. In addition to samples from the MIGen (N=≈6000), WTCCC (N=≈7400), and Framingham (N=≈3700) studies, we extended this search to a larger number of common and uncommon variants by imputation into a panel of haplotypes constructed using data from the 1000 Genomes Project. Despite the widespread expression of ERα in vascular tissues, we found no evidence for involvement of common or low-frequency genetic variation throughout theESR1gene in modifying risk of CAD, either in the general population or as a function of sex.ConclusionsWe suggest that future research on the genetic basis of sex-related differences in CAD risk should initially prioritize other genes in the reproductive steroid hormone biosynthesis system.