全基因组关联分析确定了汉族人群痛风性关节炎的三个新风险位点。
Genome-wide association analysis identifies three new risk loci for gout arthritis in Han Chinese.
作者信息
Li Changgui, Li Zhiqiang, Liu Shiguo, Wang Can, Han Lin, Cui Lingling, Zhou Jingguo, Zou Hejian, Liu Zhen, Chen Jianhua, Cheng Xiaoyu, Zhou Zhaowei, Ding Chengcheng, Wang Meng, Chen Tong, Cui Ying, He Hongmei, Zhang Keke, Yin Congcong, Wang Yunlong, Xing Shichao, Li Baojie, Ji Jue, Jia Zhaotong, Ma Lidan, Niu Jiapeng, Xin Ying, Liu Tian, Chu Nan, Yu Qing, Ren Wei, Wang Xuefeng, Zhang Aiqing, Sun Yuping, Wang Haili, Lu Jie, Li Yuanyuan, Qing Yufeng, Chen Gang, Wang Yangang, Zhou Li, Niu Haitao, Liang Jun, Dong Qian, Li Xinde, Mi Qing-Sheng, Shi Yongyong
机构信息
1] Shandong Gout Clinical Medical Center, Qingdao 266003, China [2] Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
1] Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China [2] Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
出版信息
Nat Commun. 2015 May 13;6:7041. doi: 10.1038/ncomms8041.
Gout is one of the most common types of inflammatory arthritis, caused by the deposition of monosodium urate crystals in and around the joints. Previous genome-wide association studies (GWASs) have identified many genetic loci associated with raised serum urate concentrations. However, hyperuricemia alone is not sufficient for the development of gout arthritis. Here we conduct a multistage GWAS in Han Chinese using 4,275 male gout patients and 6,272 normal male controls (1,255 cases and 1,848 controls were genome-wide genotyped), with an additional 1,644 hyperuricemic controls. We discover three new risk loci, 17q23.2 (rs11653176, P=1.36 × 10(-13), BCAS3), 9p24.2 (rs12236871, P=1.48 × 10(-10), RFX3) and 11p15.5 (rs179785, P=1.28 × 10(-8), KCNQ1), which contain inflammatory candidate genes. Our results suggest that these loci are most likely related to the progression from hyperuricemia to inflammatory gout, which will provide new insights into the pathogenesis of gout arthritis.
痛风是最常见的炎性关节炎类型之一，由尿酸单钠晶体在关节及其周围沉积所致。以往的全基因组关联研究（GWAS）已鉴定出许多与血清尿酸浓度升高相关的基因位点。然而，仅高尿酸血症并不足以引发痛风性关节炎。在此，我们对汉族男性进行了一项多阶段GWAS研究，纳入4275例男性痛风患者和6272例正常男性对照（其中1255例病例和1848例对照进行了全基因组基因分型），另有1644例高尿酸血症对照。我们发现了三个新的风险位点，分别为17q23.2（rs11653176，P = 1.36×10⁻¹³，BCAS3）、9p24.2（rs12236871，P = 1.48×10⁻¹⁰，RFX3）和11p15.5（rs179785，P = 1.28×10⁻⁸，KCNQ1），这些位点包含炎性候选基因。我们的结果表明，这些位点很可能与从高尿酸血症进展为炎性痛风有关，这将为痛风性关节炎的发病机制提供新的见解。
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