Association of polymorphisms in the CRP gene with circulating C-reactive protein levels and cardiovascular events
Association of polymorphisms in the CRP gene with circulating C-reactive protein levels and cardiovascular events
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DOI：
10.1001/jama.296.22.2703
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发表时间：
2006-12-13
影响因子：
120.7
通讯作者：
Reiner, Alexander P.
中科院分区：
文献类型：
--
作者：
Lange, Leslie A.;Carlson, Christopher S.;Reiner, Alexander P.
c反应蛋白（CRP）是一种炎症蛋白，可能在心血管疾病（CVD）的发病机制中发挥作用。目的探讨CRP基因多态性是否与血浆CRP、颈动脉内膜-中膜厚度（CIMT）和CVD事件相关。在前瞻性、基于人群的心血管健康研究中，对3941名白人（欧洲裔美国人）参与者进行了4个标签单核苷酸多态性（snp） （1919A/ T、2667G/C、3872G/A、5237A/G）的基因分型，对700名年龄在65岁或以上的黑人（非洲裔美国人）参与者进行了5个标签snp（增加790A/T）的基因分型，这些参与者在研究开始前都没有心肌梗死（MI）或中风。中位随访时间为13年（1989-2003）。基线CIMT；随访期间心肌梗死、脑卒中和心血管疾病死亡率的发生率。在白人受试者中，发生了461例心肌梗死、491例卒中和490例心血管疾病相关死亡；在黑人参与者中，发生了67例急性心肌梗死、78例卒中和75例心血管疾病相关死亡。1919T和790T等位基因分别与白人和黑人参与者较高的CRP水平有关。3872A等位基因与两种人群中较低的CRP水平相关，而2667C等位基因仅与白人参与者中较低的CRP水平相关。在这两个人群中，CIMT与任何CRP基因多态性之间没有关联。在白人受试者中，1919T等位基因与TT与AA的卒中风险增加相关（风险比[HR]， 1.40； 95%可信区间[CI]， 1.06- 1.87），与心血管疾病死亡率增加相关（风险比，1.40；95%可信区间[CI]， 1.10-1.90）。在黑人参与者中，790T等位基因的纯合子与790A等位基因的纯合子相比，心肌梗死的风险增加了4倍（95% CI, 1.58-10.53）。在白人受试者中，与较低血浆CRP浓度相关的2个snp的次要等位基因（2667C和3872A）与降低心血管疾病死亡率的风险相关。结论CRP基因的遗传变异与老年人血浆CRP水平和心血管疾病风险相关。
Context C-reactive protein (CRP) is an inflammation protein that may play a role in the pathogenesis of cardiovascular disease (CVD).Objective To assess whether polymorphisms in the CRP gene are associated with plasma CRP, carotid intima-media thickness (CIMT), and CVD events.Design, Setting, and Participants In the prospective, population-based Cardiovascular Health Study, 4 tag single-nucleotide polymorphisms ( SNPs) (1919A/ T, 2667G/C, 3872G/A, 5237A/G) were genotyped in 3941 white ( European American) participants and 5 tag SNPs ( addition of 790A/T) were genotyped in 700 black ( African American) participants, aged 65 years or older, all of whom were without myocardial infarction (MI) or stroke before study entry. Median follow-up was 13 years (1989-2003).Main Outcome Measures Baseline CIMT; occurrence of MI, stroke, and CVD mortality during follow-up.Results In white participants, 461 incident MIs, 491 incident strokes, and 490 CVD-related deaths occurred; in black participants, 67 incident MIs, 78 incident strokes, and 75 CVD-related deaths occurred. The 1919T and 790T alleles were associated with higher CRP levels in white and black participants, respectively. The 3872A allele was associated with lower CRP levels in both populations, and the 2667C allele was associated with lower CRP levels in white participants only. There was no association between CIMT and any CRP gene polymorphism in either population. In white participants, the 1919T allele was associated with increased risk of stroke for TT vs AA ( hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.06- 1.87) and for CVD mortality ( HR, 1.40; 95% CI, 1.10-1.90). In black participants, homozygosity for the 790T allele was associated with a 4-fold increased risk of MI compared with homozygosity for the 790A allele ( 95% CI, 1.58-10.53). The minor alleles of the 2 SNPs associated with lower plasma CRP concentration in white participants ( 2667C and 3872A) were associated with decreased risk of CVD mortality.Conclusions Genetic variation in the CRP gene is associated with plasma CRP levels and CVD risk in older adults.