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. © The Author 2010. Published by Oxford University Press. All rights reserved.
CITATION STYLE
Okada, Y., Takahashi, A., Ohmiya, H., Kumasaka, N., Kamatani, Y., Hosono, N., … Kamatani, N. (2011). Genome-wide association study for C-reactive protein levels identified pleiotropic associations in the IL6 locus. Human Molecular Genetics, 20(6), 1224–1231. https://doi.org/10.1093/hmg/ddq551
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