An allele-specific functional SNP associated with two systemic autoimmune diseases modulates IRF5 expression by long-range chromatin loop formation

Both Systemic Lupus Erythematosus (SLE) and Systemic Sclerosis (SSc) are autoimmune diseases sharing similar genetic backgrounds. Genome-wide association studies (GWASs) have constantly disclosed numerous genetic variants conferring to both disease risks at 7q32.1, but the functional mechanisms underlying them are still largely unknown. Through a series of bioinformatics and functional analyses, we prioritized a potential independent functional SNP (rs13239597) within TNPO3 promoter region, residing in a putative enhancer element and validated that IRF5 is the distal target gene ( ∼118kb) of rs13239597, which is a key regulator involved in pathogenic autoantibody dysregulation increasing risk of both SLE and SSc.

Source: Journal of Investigative Dermatology - August 14, 2019 Category: Dermatology Authors: Hlaing Nwe Thynn, Xiao-Feng Chen, Wei-Xin Hu, Yuan-Yuan Duan, Dong-Li Zhu, Hao Chen, Nai-Ning Wang, Huan-Huan Chen, Yu Rong, Bing-Jie Lu, Man Yang, Feng Jiang, Shan-Shan Dong, Yan Guo, Tie-Lin Yang Tags: Original Article Source Type: research