title: Identification of IL18RAP/IL18R1 and IL12B as leprosy risk genes demonstrates shared pathogenesis between inflammation and infectious diseases.
abstract: Of eight leprosy susceptibility loci identified by genome-wide association studies, five have been implicated in Crohn disease, suggesting a common genetic fingerprint between leprosy and inflammatory bowel disease (IBD). Here, we conducted a multiple-stage genetic association study of 133 IBD susceptibility loci in multiple leprosy samples (totaling 4,971 leprosy cases and 5,503 controls) from a Chinese population and discovered two associations at rs2058660 on 2q12.1 (p = 4.57 × 10(-19); odds ratio [OR] = 1.30) and rs6871626 on 5q33.3 (p = 3.95 × 10(-18); OR = 0.75), implicating IL18RAP/IL18R1 and IL12B as susceptibility genes for leprosy. Our study reveals the important role of IL12/IL18-mediated transcriptional regulation of IFN-γ production in leprosy, and together with previous findings, it demonstrates the shared genetic susceptibility between infectious and inflammatory diseases.
authors.affiliation: Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, Shandong, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Astrid
authors.initials: A
authors.lastname: Irwanto
authors.forename: Hongqing
authors.initials: H
authors.lastname: Tian
authors.forename: Xi'an
authors.initials: X
authors.lastname: Fu
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Yu
authors.forename: Gongqi
authors.initials: G
authors.lastname: Yu
authors.forename: Huiqi
authors.initials: H
authors.lastname: Low
authors.forename: Tongsheng
authors.initials: T
authors.lastname: Chu
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Benqing
authors.initials: B
authors.lastname: Shi
authors.forename: Mingfei
authors.initials: M
authors.lastname: Chen
authors.forename: Yonghu
authors.initials: Y
authors.lastname: Sun
authors.forename: Chunying
authors.initials: C
authors.lastname: Yuan
authors.forename: Nan
authors.initials: N
authors.lastname: Lu
authors.forename: Jiabao
authors.initials: J
authors.lastname: You
authors.forename: Fangfang
authors.initials: F
authors.lastname: Bao
authors.forename: Jinghui
authors.initials: J
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Huaxu
authors.initials: H
authors.lastname: Liu
authors.forename: Dianchang
authors.initials: D
authors.lastname: Liu
authors.forename: Xiulu
authors.initials: X
authors.lastname: Yu
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.forename: Guiye
authors.initials: G
authors.lastname: Niu
authors.forename: Shanshan
authors.initials: S
authors.lastname: Ma
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Chuan
authors.initials: C
authors.lastname: Wang
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: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis; D053762:Interleukin-12 Subunit p40 / Q000235:genetics*; D053727:Interleukin-18 Receptor alpha Subunit / Q000235:genetics*; D007918:Leprosy / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40; D053727:Interleukin-18 Receptor alpha Subunit; D007371:Interferon-gamma