Association of Common CRP Gene Variants with CRP Levels and Cardiovascular Events

Summary 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...

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Bibliographic Details
Published in:Annals of human genetics 2005-11, Vol.69 (6), p.623-638
Main Authors: Miller, D. T., Zee, R. Y. L., Suk Danik, J., Kozlowski, P., Chasman, D. I., Lazarus, R., Cook, N. R., Ridker, P. M., Kwiatkowski, D. J.
Format: Article
Language:English
Subjects:
Association Study
Atherosclerosis
Atherosclerosis - genetics
C-Reactive Protein - genetics
C-Reactive Protein - metabolism
Case-Control Studies
Cohort Studies
CRP
C‐reactive protein
Female
Genotype
Haplotype analysis
Humans
Male
Middle Aged
Myocardial infarction
Polymorphism, Single Nucleotide
Prospective Studies
Risk Factors
Women's Health
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Summary:Summary 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.
ISSN:0003-4800
1469-1809
DOI:10.1111/j.1529-8817.2005.00210.x