Variation in inflammation-related genes and risk of incident nonfatal myocardial infarction or ischemic stroke
Variation in inflammation-related genes and risk of incident nonfatal myocardial infarction or ischemic stroke
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DOI：
10.1016/j.atherosclerosis.2007.09.031
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发表时间：
2008-05-01
期刊：
影响因子：
5.3
通讯作者：
Psaty, Bruce M.
中科院分区：
文献类型：
--
作者：
Bis, Joshua C.;Heckbert, Susan R.;Psaty, Bruce M.
背景：从斑块形成到斑块破裂，免疫系统成分参与动脉粥样硬化。我们研究了炎症相关基因-白细胞介素（IL）-1 β、IL-6、C-反应蛋白（CRP）、IL-10、IL-18和肿瘤坏死因子（TNF）超家族[α-光敏素（LT）-α、TNF-α、LT-β] -的变异与非致命性心肌梗死（MI）或缺血性卒中风险的关系。一项基于人群的病例对照研究招募了年龄在30-79岁的绝经后和/或高血压组健康成员。我们选择了一个子集的单核苷酸多态性（SNPs）来描述常见的基因范围内的连锁不平衡的基础上的变化。在856例MI患者、368例卒中患者和2688例对照中，对36个SNP进行了基因分型，这些SNP描述了5个基因的38种常见单倍型和一个3基因簇。SNP或相位推断的单倍型和风险的关联使用逻辑回归进行估计;基因水平关联的显著性使用整体Wald检验和排列检验进行评估。全基因IL-18变异与较高的MI风险相关，而IL-1B单倍型与较低的卒中风险相关。在SNPs的二次分析中，我们观察到几种IL-1B多态性与MI或卒中风险的相关性。IL-6，CRP，IL-10，和TNF超家族基因变异与MI或中风risk.Conclusions：我们的研究结果支持以前的报告关联IL-18基因变异和M1的风险，贡献额外的证据报告IL-1B和心血管疾病的风险，并未能确认风险差异先前观察到的CRP，IL-6，和TNF-α启动子变异。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
Background: From initiation to plaque rupture, immune system components contribute to atherosclerosis. We investigated variation in inflammation-related genes - interleukin (IL)-1 beta, IL-6, C-reactive protein (CRP), IL-10, IL-18, and the tumor necrosis factor (TNF) superfamily [lymphotoxin(LT)-alpha, TNF-alpha, LT-beta] - with respect to nonfatal incident myocardial infarction (MI) or ischemic stroke risk.Methods and results: A population-based case-control study recruited postmenopausal and/or hypertensive Group Health members aged 30-79 years. We chose a subset of single nucleotide polymorphisms (SNPs) to describe common gene-wide variation on the basis of linkage disequilibrium. 36 SNPs, describing 38 common haplotypes for 5 genes and a 3-gene cluster, were genotyped among 856 MI cases, 368 stroke cases, and 2688 controls. Associations of SNPs or PHASE-inferred haplotypes and risk were estimated using logistic regression; significance of gene-level associations was assessed with global Wald tests and permutation tests. Gene-wide IL-18 variation was associated with higher MI risk and an IL-1B haplotype was associated with lower stroke risk. In secondary analyses of SNPs, we observed associations of several IL-1B polymorphisms with risk of MI or stroke. IL-6, CRP, IL-10, and TNF superfamily gene variation was not associated with MI or stroke risk.Conclusions: Our results support prior reports associating an IL-18 gene variant and M1 risk, contribute additional evidence to reports of IL-1B and cardiovascular risk, and fail to confirm risk differences previously observed for CRP, IL-6, and TNF-a promoter variants. (c) 2007 Elsevier Ireland Ltd. All rights reserved.