TY - JOUR
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
Y1 - 2011/3
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.
AB - 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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U2 - 10.1093/hmg/ddq551
DO - 10.1093/hmg/ddq551
M3 - Article
C2 - 21196492
AN - SCOPUS:79952019307
SN - 0964-6906
VL - 20
SP - 1224
EP - 1231
JO - Human molecular genetics
JF - Human molecular genetics
IS - 6
M1 - ddq551
ER -