Genome-wide association study for C-reactive protein levels identified pleiotropic associations in the IL6 locus

Hum Mol Genet. 2011 Mar 15;20(6):1224-31. doi: 10.1093/hmg/ddq551. Epub 2010 Dec 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asian Continental Ancestry Group / genetics*
  • C-Reactive Protein / metabolism*
  • Case-Control Studies
  • Female
  • Genome-Wide Association Study*
  • Genotype
  • Humans
  • Inflammation / blood
  • Inflammation / genetics*
  • Interleukin-6 / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*

Substances

  • Interleukin-6
  • C-Reactive Protein