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与C反应蛋白水平和冠心病风险相关的基因位点
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Genetic Loci Associated With C-Reactive Protein Levels and Risk of Coronary Heart Disease
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Elliott P, Chambers JC, Zhang W
2010/1/28 17:09:52
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打印|
推荐给好友
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JAMA,
2009,
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View at Publisher
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Context:
Plasma levels of C-reactive protein (CRP) are independently associated with risk of coronary heart disease, but whether CRP is causally associated with coronary heart disease or merely a marker of underlying atherosclerosis is uncertain.
Objective:
To investigate association of genetic loci with CRP levels and risk of coronary heart disease.
Design, Setting, and Participants:
We first carried out a genome-wide association (n=17 967) and replication study (n=13 615) to identify genetic loci associated with plasma CRP concentrations. Data collection took place between 1989 and 2008 and genotyping between 2003 and 2008. We carried out a mendelian randomization study of the most closely associated single-nucleotide polymorphism (SNP) in the CRP locus and published data on other CRP variants involving a total of 28 112 cases and 100 823 controls, to investigate the association of CRP variants with coronary heart disease. We compared our finding with that predicted from meta-analysis of observational studies of CRP levels and risk of coronary heart disease. For the other loci associated with CRP levels, we selected the most closely associated SNP for testing against coronary heart disease among 14 365 cases and 32 069 controls.
Main Outcome Measure:
Risk of coronary heart disease.
Results:
Polymorphisms in 5 genetic loci were strongly associated with CRP levels (% difference per minor allele): SNP rs6700896 in LEPR (−14.8%; 95% confidence interval [CI], −17.6% to −12.0%; P=6.2×10−22), rs4537545 in IL6R (−11.5%; 95% CI, −14.4% to −8.5%; P=1.3×10−12), rs7553007 in the CRP locus (−20.7%; 95% CI, −23.4% to −17.9%; P=1.3×10−38), rs1183910 in HNF1A (−13.8%; 95% CI, −16.6% to −10.9%; P=1.9×10−18), and rs4420638 in APOE-CI-CII (−21.8%; 95% CI, −25.3% to −18.1%; P=8.1×10−26). Association of SNP rs7553007 in the CRP locus with coronary heart disease gave an odds ratio (OR) of 0.98 (95% CI, 0.94 to 1.01) per 20% lower CRP level. Our mendelian randomization study of variants in the CRP locus showed no association with coronary heart disease: OR, 1.00; 95% CI, 0.97 to 1.02; per 20% lower CRP level, compared with OR, 0.94; 95% CI, 0.94 to 0.95; predicted from meta-analysis of the observational studies of CRP levels and coronary heart disease (z score, −3.45; P<.001). SNPs rs6700896 in LEPR (OR, 1.06; 95% CI, 1.02 to 1.09; per minor allele), rs4537545 in IL6R (OR, 0.94; 95% CI, 0.91 to 0.97), and rs4420638 in the APOE-CI-CII cluster (OR, 1.16; 95% CI, 1.12 to 1.21) were all associated with risk of coronary heart disease.
Conclusion:
The lack of concordance between the effect on coronary heart disease risk of CRP genotypes and CRP levels argues against a causal association of CRP with coronary heart disease.
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疾病资源中心
病例分析 [栏目介绍]
曹晶珠 邹大进
解放军第二军医大学附属长海医院内分泌科
患者为中年女性，35岁，因“多饮、多尿、全身乏力、闭经1年，体重增加、肝区不适半年”于2008年8月入院。患者2007年感冒后出现多饮、多尿，每日饮水约10,000 ml，未予重视及诊治。2007年出现闭经，在外院妇产科就诊，先后予2次黄体酮肌肉注射，仍未来月经。半年前体重增加25 kg，肝区不适，肝功能示转氨酶升高。患者无便秘腹胀、无皮肤感染、无双下肢水肿，活动后稍感胸闷、气喘，夜尿增多，平均每小时1次。最大体重88.7 kg。既往史无特殊。月经史：初潮14岁，4/28～30，2008年6月。
医学数据库
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