Association of common CRP gene variants with CRP levels and cardiovascular events

D. T. Miller, R. Y.L. Zee, J. Suk Danik, P. Kozlowski, D. I. Chasman, R. Lazarus, N. R. Cook, P. M. Ridker, David J. Kwiatkowski

Research output: Contribution to journalArticlepeer-review

200 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)623-638
Number of pages16
JournalAnnals of Human Genetics
Volume69
Issue number6
DOIs
StatePublished - Nov 2005
Externally publishedYes

Keywords

  • Association study
  • Atherosclerosis
  • C-reactive protein
  • CRP
  • Haplotype analysis
  • Myocardial infarction

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