Identification of IL18RAP/IL18R1 and IL12B as Leprosy Risk Genes Demonstrates Shared Pathogenesis between Inflammation and Infectious Diseases

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

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.

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