Mapping leprosy‐associated coding variants of interleukin genes by targeted sequencing

• Published in: Clinical genetics Vol. 99; no. 6; pp. 802 - 811
• Main Authors: Zhang, Deng‐Feng, Li, Hui‐Long, Zheng, Quanzhen, Bi, Rui, Xu, Min, Wang, Dong, Zhu, Guo‐Ping, Li, Yu‐Ye, Yao, Yong‐Gang
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2021
• Subjects: Asians - genetics; Blood cells; Case-Control Studies; China; coding variants; Female; Gene expression; Gene mapping; Genetic Predisposition to Disease - genetics; genetic susceptibility; Genotyping; Humans; interleukin; Interleukin 1; Interleukin 27; Interleukins - genetics; Leprosy; Leprosy - genetics; Male; Middle Aged; next generation sequencing; Polymorphism, Single Nucleotide - genetics; RNA, Messenger - genetics; Skin diseases; Skin lesions; China; coding variants; leprosy; genetic susceptibility; interleukin; next generation sequencing
• ISSN: 0009-9163; 1399-0004; 1399-0004
• DOI: 10.1111/cge.13945

Previous genotyping‐based assays have identified non‐coding variants of several interleukins (ILs) being associated with genetic susceptibility to leprosy. However, understanding of the involvement of coding variants within all IL family genes in leprosy was still limited. To obtain the full mutation spectrum of all ILs in leprosy, we performed a targeted deep sequencing of coding regions of 58 ILs genes in 798 leprosy patients (age 56.2 ± 14.4; female 31.5%) and 990 healthy controls (age 38.1 ± 14.0; female 44.3%) from Yunnan, Southwest China. mRNA expression alterations of ILs in leprosy skin lesions or in response to M. leprae treatment were estimated by using publicly available expression datasets. Two coding variants in IL27 (rs17855750, p.S59A, p = 4.02 × 10−8, odds ratio [OR] = 1.748) and IL1RN (rs45507693, p.A106T, p = 1.45 × 10−5, OR = 3.629) were significantly associated with leprosy risk. mRNA levels of IL27 and IL1RN were upregulated in whole blood cells after M. leprae stimulation. These data showed that IL27 and IL1RN are leprosy risk genes. Further functional study is required for characterizing the exact role of ILs in leprosy. Leprosy is a chronic infectious caused by Mycobacterium leprae. Genetic studies have identified non‐coding vartiants of interleukin genes affecting the susceptibility to leprosy. We investigated the complete mutation spectrum of all interleukin family genes in subjects with and without leprosy by using targeted next‐generation sequencing. We found a strong association of coding variants in IL27 and IL1 signaling genes with leprosy.