CCL2 polymorphisms are associated with serum monocyte chemoattractant protein-1 levels and myocardial infarction in the framingham heart study
CCL2 polymorphisms are associated with serum monocyte chemoattractant protein-1 levels and myocardial infarction in the framingham heart study
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DOI：
10.1161/circulationaha.105.543579
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发表时间：
2005-08-23
期刊：
影响因子：
37.8
通讯作者：
Benjamin, EJ
中科院分区：
文献类型：
--
作者：
McDermott, DH;Yang, Q;Benjamin, EJ
背景-单核细胞趋化蛋白-1(MCP-1)是一种趋化因子，在动物模型中强烈参与促进动脉粥样硬化，但人类的遗传学证据是相互矛盾的。方法和结果-我们分析了社区Framingham心脏研究后代队列(50%女性；平均年龄，62岁)MCP-1基因(CCL2)的遗传变异与心肌梗死和血清MCP-1水平的关系。分别检测3236人和1797人的MCP-1水平和CCL2基因分型。MCP-1水平的显著临床相关性是年龄、吸烟、甘油三酯、体重指数和腰臀比。位于CCL2调控区的单核细胞趋化蛋白-1-2578G等位基因与隐性遗传模型中较高的血清单核细胞趋化蛋白-1水平(358+/-10对328+/-3pg/mL；P=0.002)和显性遗传模型中较高的心肌梗死患病率(调整后的优势比为2.0；95%可信区间为1.20~3.3；P=0.005)显著相关。我们还定义了CCL2基因座的连锁不平衡结构，观察到了白种常见的6种单倍型。我们进行了基于单倍型的关联分析，发现只有由MCP-1-2578G等位基因定义的最常见的单倍型与流行的MI相关。结论-我们的数据与MCP-1参与人类动脉粥样硬化和心肌梗死发病机制的假设是一致的。
Background - Monocyte chemoattractant protein-1 (MCP-1) is a chemokine strongly implicated in promoting atherosclerosis in animal models, but human genetic evidence is contradictory.Methods and Results - We analyzed the association of genetic variation in the MCP-1 gene (CCL2) with prevalent myocardial infarction and serum MCP-1 levels in the community-based Framingham Heart Study Offspring Cohort (50% women; mean age, 62 years). MCP-1 levels and CCL2 genotypes were determined in 3236 and 1797 individuals, respectively. Significant clinical correlates of MCP-1 levels were age, cigarette smoking, triglycerides, body mass index, and waist-to-hip ratio. The MCP-1-2578G allele located in the CCL2 regulatory region was significantly associated with both higher serum MCP-1 levels in a recessive genetic model (358 +/- 10 versus 328 +/- 3 pg/mL; P = 0.002) and higher prevalence of myocardial infarction in a dominant genetic model (adjusted odds ratio, 2.0; 95% CI, 1.2 to 3.3; P = 0.005). We also defined the linkage disequilibrium structure at the CCL2 locus and observed 6 common haplotypes in whites. We performed haplotype-based association analysis and found that only the most frequent haplotype, defined by the MCP-1-2578G allele, was associated with prevalent MI.Conclusions - Our data are consistent with the hypothesis that MCP-1 is involved in the pathogenesis of human atherosclerosis and myocardial infarction.