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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.

More information

Type
Journal Article
Author
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