Relation of Genetic Variation in the Gene Coding for C-Reactive Protein with Its Plasma Protein Concentrations: Findings from the Women's Health Initiative Observational Cohort

BACKGROUND: Although common genetic variants of the CRP gene (C-reactive protein, pentraxin related) have been associated with plasma concentrations of high-sensitivity CRP (hsCRP) in several cohorts of European Americans, relatively few studies have comprehensively assessed this association in well-characterized multiethnic populations. METHODS: In a case-control study of diabetes nested in the Women's Health initiative Observational Cohort, we comprehensively evaluated the association of genetic variation in CRP with plasma hsCRP concentrations. Thirteen haplotype-tagging single-nucleotide polymorphisms (tSNPs) were identified and subsequently genotyped in 3782 postmenopausal women. RESULTS: The allele frequencies for these tSNPs and the haplotype blocks defined by these tSNPs varied significantly by ethnic group (P < 0.0001). Consistent with prior studies of whites, rs3093068, rs1130864, and rs1417938 were significantly associated with higher hsCRP concentrations (geometric-mean increase per minor-allele change, 1.20-1.25 mg/L), and rs1205 and rs1800947 were significantly associated with lower hsCRP values (decrease of 1.28-1.48 mg/L). The associations with rs3093068 and rs1205 appeared to be stronger in Asians/Pacific Islanders than in whites (geometric-mean increase, 1.65 mg/L vs 1.25 mg/L, respectively). Minor alleles at rs3093075 and rs3093039 were associated with substantially increased hsCRP concentrations, whereas rs1800947 was associated with lower hsCRP values. All haplotype-based association results tended to be consistent with the associations seen with single CRP SNPs. CONCLUSIONS: Our large multiethnic case-control study of postmenopausal women provides evidence that common genetic variants in the CRP gene are substantially associated with plasma hsCRP concentrations in this case-control subcohort. The data also suggest ethnic variations in these associations. (C) 2008 American Association for Clinical Chemistry