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Genome-wide association study for C-reactive protein levels identified pleiotropic associations in the IL6 locus.
- Source :
-
Human molecular genetics [Hum Mol Genet] 2011 Mar 15; Vol. 20 (6), pp. 1224-31. Date of Electronic Publication: 2010 Dec 31. - Publication Year :
- 2011
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Abstract
- C-reactive protein (CRP) is a hallmark acute-phase reactant and is widely used as a blood marker for inflammation. Substantial roles of serum CRP levels in the pathogenesis of diseases have been suggested, and investigation of the mechanisms that regulate serum CRP levels would have a substantial clinical impact. Here, through genome-wide association and replication studies performed using 12 854 Japanese subjects, we identified a significant association between serum CRP levels and a single nucleotide polymorphism in the promoter region of interleukin-6 (IL6) (rs2097677, P = 4.1 × 10(-11)), a typical pleiotropic pro-inflammatory cytokine. Our study also replicated the associations in the CRP (rs3093059, P = 3.5 × 10(-21)) and HNF1A loci (rs7310409, P = 2.7 × 10(-8)). Pleiotropic association analysis with hematological and biochemical traits using 30 466 Japanese subjects demonstrated that the CRP-increasing allele of rs2097677 in the IL6 locus was significantly associated with an increased white blood cell count, platelet count and serum globulin and a decreased mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration (P < 5.0 × 10(-4)), although no pleiotropic association was observed in the CRP or HNF1A locus (α = 0.01). Our study demonstrated the pivotal role of the IL6 locus in the regulation of serum CRP levels and inflammatory pathways.
Details
- Language :
- English
- ISSN :
- 1460-2083
- Volume :
- 20
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Human molecular genetics
- Publication Type :
- Academic Journal
- Accession number :
- 21196492
- Full Text :
- https://doi.org/10.1093/hmg/ddq551