Genomewide Association Study of Leprosy

作者：Furen Zhang, Wei Huang, Shumin Chen, Liangdan Sun, Hong Liu, Yi Li, Yong Cui, Xiaoxiao Yan, Haitao Yang, Rongde Yang, Tongsheng Chu, Chi Zhang, Lin Zhang, Jianwen Han, Gongqi Yu, Cheng Quan, Yongxiang Yu, Zheng Zhang, Benqing Shi, Lianhua Zhang, Hui Cheng, Changyuan Wang, Yan Lin, Hou‐Feng Zheng, Xi’an Fu, Xian-Bo Zuo, Qiang Wang, Heng Long, Yiping Sun, Yi‐Lin Cheng, Hongqing Tian, Fusheng Zhou, Huaxu Liu, Wensheng Lu, Su-Min He, Wenli Du, Min Shen, Qi-Yi Jin, Ying Wang, Hui-Qi Low, Erwin Tantoso, Ninghan Yang, Jinyong Li, Xin Zhao, Yue-Lin Jiao, Liguo Mao, Gang Yin, Zhenxia Jiang, Xiaodong Wang, Jingping Yu, Zong-Hou Hu, Cui-Hua Gong, Yuqiang Liu, Ruiyu Liu, Demin Wang, Dong Wei, Jinxian Liu, Wei-Kun Cao, Hong-Zhong Cao, Yongping Li, Weiguo Yan, Shiyu Wei, Kui-Jun Wang, Martin L. Hibberd, Sen Yang, Xue-Jun Zhang, Jianjun Liu · 发表于：New England Journal of Medicine · 年份：2009 · DOI：10.1056/nejmoa0903753 · 被引用次数：1053 · 研究领域：Leprosy Research and Treatment、Tuberculosis Research and Epidemiology、Fibromyalgia and Chronic Fatigue Syndrome Research

BACKGROUND: The narrow host range of Mycobacterium leprae and the fact that it is refractory to growth in culture has limited research on and the biologic understanding of leprosy. Host genetic factors are thought to influence susceptibility to infection as well as disease progression. METHODS: We performed a two-stage genomewide association study by genotyping 706 patients and 1225 controls using the Human610-Quad BeadChip (Illumina). We then tested three independent replication sets for an association between the presence of leprosy and 93 single-nucleotide polymorphisms (SNPs) that were most strongly associated with the disease in the genomewide association study. Together, these replication sets comprised 3254 patients and 5955 controls. We also carried out tests of heterogeneity of the associations (or lack thereof) between these 93 SNPs and disease, stratified according to clinical subtype (multibacillary vs. paucibacillary). RESULTS: We observed a significant association (P<1.00x10(-10)) between SNPs in the genes CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR, and RIPK2 and a trend toward an association (P=5.10x10(-5)) with a SNP in LRRK2. The associations between the SNPs in C13orf31, LRRK2, NOD2, and RIPK2 and multibacillary leprosy were stronger than the associations between these SNPs and paucibacillary leprosy. CONCLUSIONS: Variants of genes in the NOD2-mediated signaling pathway (which regulates the innate immune response) are associated with susceptibility to infectio...