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

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

Research output: Contribution to journalArticle

52 Citations (Scopus)

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.

Original languageEnglish
Article numberddq551
Pages (from-to)1224-1231
Number of pages8
JournalHuman Molecular Genetics
Volume20
Issue number6
DOIs
Publication statusPublished - 01-03-2011
Externally publishedYes

Fingerprint

Genome-Wide Association Study
C-Reactive Protein
Interleukin-6
Blood Proteins
Erythrocyte Indices
Serum Globulins
Acute-Phase Proteins
Platelet Count
Leukocyte Count
Genetic Promoter Regions
Single Nucleotide Polymorphism
Alleles
Cytokines
Inflammation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

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. [ddq551]. https://doi.org/10.1093/hmg/ddq551
Okada, Yukinori ; Takahashi, Atsushi ; Ohmiya, Hiroko ; Kumasaka, Natsuhiko ; Kamatani, Yoichiro ; Hosono, Naoya ; Tsunoda, Tatsuhiko ; Matsuda, Koichi ; Tanaka, Toshihiro ; Kubo, Michiaki ; Nakamura, Yusuke ; Yamamoto, Kazuhiko ; Kamatani, Naoyuki. / Genome-wide association study for C-reactive protein levels identified pleiotropic associations in the IL6 locus. In: Human Molecular Genetics. 2011 ; Vol. 20, No. 6. pp. 1224-1231.
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author = "Yukinori Okada and Atsushi Takahashi and Hiroko Ohmiya and Natsuhiko Kumasaka and Yoichiro Kamatani and Naoya Hosono and Tatsuhiko Tsunoda and Koichi Matsuda and Toshihiro Tanaka and Michiaki Kubo and Yusuke Nakamura and Kazuhiko Yamamoto and Naoyuki Kamatani",
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Okada, Y, Takahashi, A, Ohmiya, H, Kumasaka, N, Kamatani, Y, Hosono, N, Tsunoda, T, Matsuda, K, Tanaka, T, Kubo, M, Nakamura, Y, Yamamoto, K & Kamatani, N 2011, 'Genome-wide association study for C-reactive protein levels identified pleiotropic associations in the IL6 locus', Human Molecular Genetics, vol. 20, no. 6, ddq551, pp. 1224-1231. https://doi.org/10.1093/hmg/ddq551

Genome-wide association study for C-reactive protein levels identified pleiotropic associations in the IL6 locus. / Okada, Yukinori; Takahashi, Atsushi; Ohmiya, Hiroko; Kumasaka, Natsuhiko; Kamatani, Yoichiro; Hosono, Naoya; Tsunoda, Tatsuhiko; Matsuda, Koichi; Tanaka, Toshihiro; Kubo, Michiaki; Nakamura, Yusuke; Yamamoto, Kazuhiko; Kamatani, Naoyuki.

In: Human Molecular Genetics, Vol. 20, No. 6, ddq551, 01.03.2011, p. 1224-1231.

Research output: Contribution to journalArticle

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T1 - Genome-wide association study for C-reactive protein levels identified pleiotropic associations in the IL6 locus

AU - Okada, Yukinori

AU - Takahashi, Atsushi

AU - Ohmiya, Hiroko

AU - Kumasaka, Natsuhiko

AU - Kamatani, Yoichiro

AU - Hosono, Naoya

AU - Tsunoda, Tatsuhiko

AU - Matsuda, Koichi

AU - Tanaka, Toshihiro

AU - Kubo, Michiaki

AU - Nakamura, Yusuke

AU - Yamamoto, Kazuhiko

AU - Kamatani, Naoyuki

PY - 2011/3/1

Y1 - 2011/3/1

N2 - 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.

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