Genome-wide association study for C-reactive protein levels identified pleiotropic associations in the IL6 locus
Genome-wide association study for C-reactive protein levels identified pleiotropic associations in the IL6 locus
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DOI：
10.1093/hmg/ddq551
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发表时间：
2011-03-15
影响因子：
3.5
通讯作者：
Kamatani, Naoyuki
中科院分区：
文献类型：
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作者：
Okada, Yukinori;Takahashi, Atsushi;Kamatani, Naoyuki
C-反应蛋白（CRP）是一种标志性的急性期反应物，被广泛用作炎症的血液标志物。血清CRP水平在疾病发病机制中的重要作用已经被提出，并且对调节血清CRP水平的机制的研究将具有重要的临床影响。在此，通过对12854名日本受试者进行的全基因组关联和复制研究，我们确定了血清CRP水平与白细胞介素6（IL 6）启动子区单核苷酸多态性（rs 2097677，P = 4.1 x 10（-11））之间的显著关联，IL 6是一种典型的多效性促炎细胞因子。我们的研究还重复了CRP（rs3093059，P = 3.5 x 10（-21））和HNF 1A位点（rs7310409，P = 2.7 x 10（-8））的相关性。对30 466名日本受试者进行的血液学和生化性状的多效性关联分析表明，IL 6基因座中的CRP增加等位基因rs 2097677与白色血细胞计数、血小板计数和血清球蛋白增加以及平均红细胞血红蛋白和平均红细胞血红蛋白浓度降低显著相关（P < 5.0 × 10 - 4），尽管在CRP或HNF 1A位点没有观察到多效性相关（α = 0.01）。我们的研究证明了IL 6位点在调节血清CRP水平和炎症途径中的关键作用。
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 x 10(-11)), a typical pleiotropic pro-inflammatory cytokine. Our study also replicated the associations in the CRP (rs3093059, P = 3.5 x 10(-21)) and HNF1A loci (rs7310409, P = 2.7 x 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 x 10(-4)), although no pleiotropic association was observed in the CRP or HNF1A locus (alpha = 0.01). Our study demonstrated the pivotal role of the IL6 locus in the regulation of serum CRP levels and inflammatory pathways.