title: An association study of TOLL and CARD with leprosy susceptibility in Chinese population.
abstract: 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.
authors.affiliation: Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Shandong, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Fangfang
authors.initials: F
authors.lastname: Bao
authors.forename: Astrid
authors.initials: A
authors.lastname: Irwanto
authors.forename: Xi'an
authors.initials: X
authors.lastname: Fu
authors.forename: Nan
authors.initials: N
authors.lastname: Lu
authors.forename: Gongqi
authors.initials: G
authors.lastname: Yu
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Yu
authors.forename: Yonghu
authors.initials: Y
authors.lastname: Sun
authors.forename: Huiqi
authors.initials: H
authors.lastname: Low
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Herty
authors.initials: H
authors.lastname: Liany
authors.forename: Chunying
authors.initials: C
authors.lastname: Yuan
authors.forename: Jinghui
authors.initials: J
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Mingfei
authors.initials: M
authors.lastname: Chen
authors.forename: Huaxu
authors.initials: H
authors.lastname: Liu
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.forename: Jiabao
authors.initials: J
authors.lastname: You
authors.forename: Shanshan
authors.initials: S
authors.lastname: Ma
authors.forename: Guiye
authors.initials: G
authors.lastname: Niu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Tongsheng
authors.initials: T
authors.lastname: Chu
authors.forename: Hongqing
authors.initials: H
authors.lastname: Tian
authors.forename: Shumin
authors.initials: S
authors.lastname: Chen
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.forename: Furen
authors.initials: F
authors.lastname: Zhang
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D044466:Asian People / Q000235:genetics; D000074018:B-Cell CLL-Lymphoma 10 Protein; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007918:Leprosy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051193:Toll-Like Receptors / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D053468:CARD Signaling Adaptor Proteins; D051193:Toll-Like Receptors