期刊
ANNALS OF HUMAN GENETICS
卷 69, 期 -, 页码 623-638出版社
WILEY
DOI: 10.1111/j.1529-8817.2005.00210.x
关键词
Association Study; atherosclerosis; C-reactive protein; CRP; haplotype analysis; myocardial infarction
资金
- NHLBI NIH HHS [HL 58755, HL 43851, HL 63293, 1F32 HL 78274-01] Funding Source: Medline
C-reactive protein (CRP) is a well-documented marker of atherosclerotic cardiovascular disease risk. We resequenced CRP to identify a comprehensive set of common SNP variants, then studied and replicated their association with baseline CRP level among apparently healthy subjects in the Women's Health Study (WHS; n = 717), Pravastatin Inflammation/CRP Evaluation trial (PRINCE; n = 1,110) and Physicians' Health Study (PHS; n = 509) cohorts. The minor alleles of four SNPs were consistently associated in all three cohorts with higher CRP, while the minor alleles of two SNPs were associated with lower CRP (p < 0.05 for each). Single marker and haplotype analysis in all three cohorts were consistent with functional roles for the 5'-flanking triallelic SNP -286C > T > A and the 3'-UTR SNP 1846G > A. None of the SNPs associated with higher CRP were associated with risk of incident myocardial infarction (MI) or ischemic stroke in a prospective, nested case-control study design from the PHS cohort (610 case-control pairs). One SNP, -717A > G, was unrelated to CRP levels but associated with decreased risk of MI (p = 0.001). Taken together, these data imply significant interactions between both genetic and environmental contributions to the increased CRP levels that predict a greater risk of future atherothrombotic events in epidemiological studies.
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