An association study of TOLL and CARD with leprosy susceptibility in Chinese population

An association study of TOLL and CARD with leprosy susceptibility in Chinese population

Human Molecular Genetics

10.1093/hmg/ddt286

http://www.hmg.oxfordjournals.org/cgi/doi/10.1093/hmg/ddt286

F. Zhang, H. Liu, F. Bao, A. Irwanto, X. Fu, N. Lu, G. Yu, Y. Yu, Y. Sun, H. Low, Y. Li, H. Liany, C. Yuan, J. Li, J. Liu, M. Chen, N. Wang, J. You, S. Ma, G. Niu, Y. Zhou, T. Chu, H. Tian, S. Chen, X. Zhang

19 June 2013

Hong Liu, Fangfang Bao, Astrid Irwanto, Xi'an Fu, Nan Lu, Gongqi Yu, Yongxiang Yu, Yonghu Sun, Huiqi Low, Yi Li, Herty Liany, Chunying Yuan, Jinghui Li, Jian Liu, Mingfei Chen, Huaxu Liu, Na Wang, Jiabao You, Shanshan Ma, Guiye Niu, Yan Zhou, Tongsheng Chu, Hongqing Tian, Shumin Chen, Xuejun Zhang, Jianjun Liu, and Furen Zhang An association study of TOLL and CARD with leprosy susceptibility in Chinese population Hum. Mol. Genet. (2013) 22 (21): 4430-4437 first published online June 19, 2013 doi:10.1093/hmg/ddt286

Previous genome-wide association studies (GWASs) identified multiple susceptibility loci that have highlighted the important role of TLR (Toll-like receptor) and CARD (caspase recruitment domain) genes in leprosy. A large three-stage candidate gene-based association study of 30 TLR and 47 CARD genes was performed in the leprosy samples of Chinese Han. Of 4363 SNPs investigated, eight SNPs showed suggestive association (P < 0.01) in our previously published GWAS datasets (Stage 1). Of the eight SNPs, rs2735591 and rs4889841 showed significant association (P < 0.001) in an independent series of 1504 cases and 1502 controls (Stage 2), but only rs2735591 (next to BCL10) showed significant association in the second independent series of 938 cases and 5827 controls (Stage 3). Rs2735591 showed consistent association across the three stages (P > 0.05 for heterogeneity test), significant association in the combined validation samples (Pcorrected = 5.54 × 10(-4) after correction for 4363 SNPs tested) and genome-wide significance in the whole GWAS and validation samples (P = 1.03 × 10(-9), OR = 1.24). In addition, we demonstrated the lower expression of BCL10 in leprosy lesions than normal skins and a significant gene connection between BCL10 and the eight previously identified leprosy loci that are associated with NFκB, a major regulator of downstream inflammatory responses, which provides further biological evidence for the association. We have discovered a novel susceptibility locus on 1p22, which implicates BCL10 as a new susceptibility gene for leprosy. Our finding highlights the important role of both innate and adaptive immune responses in leprosy.

https://oar.a-star.edu.sg/communities-collections/articles/11905

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Genome Institute of Singapore