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

Abstract

SummaryC-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.

C-reactive protein (CRP) gene polymorphisms, CRP levels and risk of incident essential hypertension: findings from an observational cohort of Han Chinese

“…Although studies that assessed common variation and haplotypes in the CRP gene with plasma CRP levels have used different SNP selection and haplotype estimation methodologies, our study confirmed previous reports of the association of plasma CRP with genetic variants, especially that the minor alleles of rs1205 and rs1800947 are associated with lower CRP levels and that the minor allele of rs1130864 is associated with higher CRP levels. 12,[15][16][17]21 Moreover, we found that the G allele of rs2246469 was associated with lower CRP levels in Han Chinese.…”

“…Increased circulating concentrations of high-sensitivity CRP (hsCRP) have been associated with a panel of clinical endpoints, such as obesity, diabetes mellitus, 3-5 hypertension 2,6-8 and atherosclerotic cardiovascular disease. [9][10][11][12][13] The reported heritability estimates of CRP range from 27 to 40%. Common genetic variants in the CRP gene were found to be associated with plasma hsCRP levels, 11,[13][14][15][16] and this association may vary in different ethnic groups.…”

C-reactive protein haplotype is associated with high PSA as a marker of metastatic prostate cancer but not with overall cancer risk

“…The haplotype ACCCA and some of its alleles have previously been associated with low CRP levels in Finns (Eklund et al, 2008) as well as in other populations, (Carlson et al, 2005;Miller et al, 2005;Crawford et al, 2006;Suk Danik et al, 2006) although not all of the SNPs of the haplotypes used in these studies were exactly the same. According to a recent meta-analysis with well-adjusted CRP values, systemic CRP concentrations seem not to be associated with PC as such (Heikkila et al, 2007).…”

CRP Polymorphisms and Progression of Chronic Kidney Disease in African Americans

“…However, our study represents an independent replication for the association of CRP polymorphisms with CRP levels (21,22,24). Independent replication studies in racially diverse CKD progression cohorts will be necessary to substantiate the new findings.…”