山东省皮肤病性病防治研究所所长张福仁率领的课题组，近期发现麻风病与炎症性肠病（IBD）共有两个新的麻风易感基因：IL18RAP/IL18R1和IL12B，并证明两个基因在这两种疾病中的风险效应相反。该项成果近日在线发表在《美国人类遗传学杂志》上。
据介绍，麻风病是由麻风分枝杆菌感染易感个体后，经过一定的潜伏期，选择性侵犯皮肤和外周神经、晚期可致残的慢性传染病；而炎症性肠病是一种慢性炎症性胃肠功能失调性疾病。
“两种病看似毫无关联，但研究显示两者间存在共同的遗传背景。”张福仁介绍说，在以往发现的8个麻风易感区域中，有5个也是炎症性肠病的易感位点。课题组由此推测，麻风和炎症性肠病可能还有更多的共有易感基因。课题组在来自中国人群的4个独立麻风样本中进行了验证，结果证实IL18RAP/IL18R1和IL12B也是麻风的易感基因。
张福仁说，在麻风易感者中，这两个基因通过一定的途径导致机体某些方面的免疫缺陷，从而增加麻风的患病风险；而在炎症性肠病中，两个基因可导致机体某些方面的免疫亢进，从而增加炎症性肠病的患病风险。
“这两个基因在麻风和炎症性肠病中所起的作用完全相反。一个人如果得了炎症性肠病，就绝不会得麻风；如果得了麻风，就绝不会再患炎症性肠病。”张福仁解释说，这种情况表明由于自然选择，机体免疫应答的增强使得传染性疾病的发生率在减少，而发生炎症性疾病的风险则会增加。
据了解，该研究有助于揭示麻风和炎症性肠病的发病机理及深入了解炎症性疾病与传染性疾病发病机制的内在联系，同时随着更多易感基因的发现，麻风病的一级预防将成为可能。（生物谷Bioon.com）
doi: 10.1016/j.ajhg.2012.09.010
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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.
