Association of common CRP gene variants with CRP levels and cardiovascular events.
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.
Miller
D T
DT
Division of Hematology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
Zee
R Y L
RY
Suk Danik
J
J
Kozlowski
P
P
Chasman
D I
DI
Lazarus
R
R
Cook
N R
NR
Ridker
P M
PM
Kwiatkowski
D J
DJ
D050197:Atherosclerosis / Q000235:genetics*; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D016387:Women's Health
D002097:C-Reactive Protein