Journal of autoimmunity · 2020
The amino acid variants in HLA II molecules explain the major association with adult-onset Still's disease in the Han Chinese population.
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Teng Jia-Lin, Chen Xia, Chen Jianhua, Zeng Ting, He Lin, Li Meihang, Luo Cai-Nan, Liu Shuang, Ding Ting-Ting, Yimaiti Kuerbanjiang, Li Xingwang, Ding Yonghe, Cheng Xiao-Bing, Zhou Juan, Ye Jun-Na, Ji Jue, Su Yu-Tong, Shi Hui, Sun Yue, Gao Chengwen, Hu Qiong-Yi, Chi Hui-Hui, Yuan Xuan, Zhou Zhuo-Chao, Wang Dong, Wang Ke, Feng Dong, Li Changgui, Sun Yuanchao, Niu Yujuan, Xu Xiaolei, Chen Lin-Jie, Xu Jian, Wu Li-Jun, Zhou Zhaowei, Pan Dun, Niu Haitao, Yang Cheng-de, Yongyong Shi, Li Zhiqiang, Liu Hong-Lei
Аннотация
Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease with systemic involvement, and its pathophysiology remains unclear. Genome-wide association studies (GWAS) in the Chinese population have revealed an association between AOSD and the major histocompatibility complex (MHC) locus; however, causal variants in the MHC remain undetermined. In the present study, we identified independent amino-acid polymorphisms in human leukocyte antigen (HLA) molecules that are associated with Han Chinese patients with AOSD by fine-mapping the MHC locus. Through conditional analyses, we identified position 34 in HLA-DQα1 (p = 1.44 × 10-14) and Asn in HLA-DRβ1 position 37 (p = 5.12 × 10-11) as the major determinants for AOSD. Moreover, we identified the associations for three main HLA class II alleles: HLA-DQB1*06:02 (OR = 2.70, p = 3.02 × 10-14), HLA-DRB1*15:01 (OR = 2.44, p = 3.66 × 10-13), and HLA-DQA1*01:02 (OR = 1.97, p = 1.09 × 10-9). This study reveals the relationship between functional variations in the class II HLA region and AOSD, implicating the MHC locus in the pathogenesis of AOSD.