Literature DB >> 19095725

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.

Cathy C Lee1, Nai-chieh Yuko You, Yiqing Song, Yi-Hsiang Hsu, JoAnn Manson, Lauren Nathan, Lesley Tinker, Simin Liu.   

Abstract

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 rs3093059 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.

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Year:  2008        PMID: 19095725      PMCID: PMC2856608          DOI: 10.1373/clinchem.2008.117176

Source DB:  PubMed          Journal:  Clin Chem        ISSN: 0009-9147            Impact factor:   8.327


  35 in total

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