Received on September 1, 2008
Accepted on November 15, 2008

Molecular Diagnostics and Genetics

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

¹ Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, and VA Greater Los Angeles Healthcare System, Los Angeles, CA
² Department of Epidemiology, UCLA, School of Public Health, Los Angeles, CA
³ Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
⁴ Molecular and Integrative Physiological Science Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA
⁵ Department of OB/GYN, David Geffen School of Medicine, UCLA, Los Angeles, CA
⁶ Fred Hutchinson Cancer Research Center, Seattle, WA
⁷ Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA; Department of Epidemiology, UCLA, School of Public Health, Los Angeles, CA, and Johnson Comprehensive Cancer Center, David Geffen School of Medicine, UCLA, Los Angeles, CA

^* To whom correspondence should be addressed. E-mail: siminliu{at}ucla.edu.

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. 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.