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

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.

• Authors: Yukinori Okada, Atsushi Takahashi, Hiroko Ohmiya, Natsuhiko Kumasaka, Yoichiro Kamatani, Naoya Hosono, Tatsuhiko Tsunoda, Koichi Matsuda, Toshihiro Tanaka, Michiaki Kubo, Yusuke Nakamura, Kazuhiko Yamamoto, Naoyuki Kamatani
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 20 Issue 6 Pg. 1224-31 (Mar 15 2011) ISSN: 1460-2083 [Electronic] England
• PMID: 21196492 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• C-Reactive Protein

Topics

• Adult
• Aged
• Asian People (genetics)
• C-Reactive Protein (metabolism)
• Case-Control Studies
• Female
• Genome-Wide Association Study
• Genotype
• Humans
• Inflammation (blood, genetics)
• Interleukin-6 (genetics)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide