山東省皮膚病性病防治研究所所長張福仁率領(lǐng)的課題組,，近期發(fā)現(xiàn)麻風(fēng)病與炎癥性腸?。↖BD）共有兩個(gè)新的麻風(fēng)易感基因：IL18RAP/IL18R1和IL12B，并證明兩個(gè)基因在這兩種疾病中的風(fēng)險(xiǎn)效應(yīng)相反,。該項(xiàng)成果近日在線發(fā)表在《美國人類遺傳學(xué)雜志》上,。
據(jù)介紹，麻風(fēng)病是由麻風(fēng)分枝桿菌感染易感個(gè)體后,，經(jīng)過一定的潛伏期,，選擇性侵犯皮膚和外周神經(jīng)、晚期可致殘的慢性傳染??；而炎癥性腸病是一種慢性炎癥性胃腸功能失調(diào)性疾病。
“兩種病看似毫無關(guān)聯(lián),，但研究顯示兩者間存在共同的遺傳背景,。”張福仁介紹說，在以往發(fā)現(xiàn)的8個(gè)麻風(fēng)易感區(qū)域中,，有5個(gè)也是炎癥性腸病的易感位點(diǎn),。課題組由此推測，麻風(fēng)和炎癥性腸病可能還有更多的共有易感基因,。課題組在來自中國人群的4個(gè)獨(dú)立麻風(fēng)樣本中進(jìn)行了驗(yàn)證,，結(jié)果證實(shí)IL18RAP/IL18R1和IL12B也是麻風(fēng)的易感基因。
張福仁說,，在麻風(fēng)易感者中,，這兩個(gè)基因通過一定的途徑導(dǎo)致機(jī)體某些方面的免疫缺陷，從而增加麻風(fēng)的患病風(fēng)險(xiǎn),；而在炎癥性腸病中,，兩個(gè)基因可導(dǎo)致機(jī)體某些方面的免疫亢進(jìn),，從而增加炎癥性腸病的患病風(fēng)險(xiǎn)。
“這兩個(gè)基因在麻風(fēng)和炎癥性腸病中所起的作用完全相反,。一個(gè)人如果得了炎癥性腸病,，就絕不會(huì)得麻風(fēng)；如果得了麻風(fēng),，就絕不會(huì)再患炎癥性腸病,。”張福仁解釋說，這種情況表明由于自然選擇,，機(jī)體免疫應(yīng)答的增強(qiáng)使得傳染性疾病的發(fā)生率在減少,，而發(fā)生炎癥性疾病的風(fēng)險(xiǎn)則會(huì)增加。
據(jù)了解,，該研究有助于揭示麻風(fēng)和炎癥性腸病的發(fā)病機(jī)理及深入了解炎癥性疾病與傳染性疾病發(fā)病機(jī)制的內(nèi)在聯(lián)系,，同時(shí)隨著更多易感基因的發(fā)現(xiàn)，麻風(fēng)病的一級(jí)預(yù)防將成為可能,。（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.
