동아시아인에서 크론병과 나병의 유전적 감수성 공유
Previous genome-wide association studies performed in Chinese patients with leprosy and in European patients with Crohn’s disease (CD) suggested that CD and leprosy might share a common underlying genetic susceptibility related to nonspecific innate immunity. There are no genome-wide scale comparisons between CD and leprosy susceptibility in Asian population.
We performed a CD meta-analysis comprising 3,566 cases and 8,885 controls of Korean, Chinese and Japanese ancestry, and a leprosy meta-analysis comprising 2,960 cases and 3,747 controls of Chinese ancestry. We then compared susceptibility loci to CD and leprosy for identification of common susceptibility loci to both diseases.
By comparing 18 CD risk loci with 19 leprosy risk loci, we identified 9 common susceptibility loci to both diseases: IL23R at 1p31.3, IL18RAP at 2q12.1, IL12B at 5q33.3, RIPK2 at 8q21.3, TNFSF15 at 9q32, ZNF365 at 10q21.2, CCDC88B at 11q13.1, LACC1 at 13q14.1, and NOD2 at 16q12.1. Of the 9 common loci, only 2 loci including LACC1 at 13q14.1 and RIPK2 at 8q21.3 showed concordance in allelic effects between CD and leprosy.
Our study showed that CD and leprosy shared about half of its genetic susceptibility in East Asians. Majority of the common susceptibility loci to CD and leprosy showed allelic effects in the opposite direction, suggesting their roles in both defense against infection and autoimmunity.
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- Crohn’s disease; leprosy; East Asian; shared genetic susceptibility
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