单倍型
医学
视神经脊髓炎
等位基因
免疫学
基因型
人类白细胞抗原
优势比
光谱紊乱
外显子组测序
遗传学
抗体
内科学
基因
突变
抗原
生物
精神科
作者
Xiaonan Zhong,Chen Chen,Xiaobo Sun,Jingqi Wang,Rui Li,Yanyu Chang,Ping Fan,Yuge Wang,Yunting Wu,Lisheng Peng,Zhengqi Lu,Wei Qiu
摘要
Abstract Background and objective Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease. Although genetic factors are involved in its pathogenesis, limited evidence is available in this area. The aim of the present study was to identify the major genetic factors contributing to NMOSD in Chinese patients with aquaporin 4 (AQP4)‐IgG seropositivity. Methods Whole‐exome sequencing (WES) was performed on 228 Chinese NMOSD patients seropositive for AQP4‐IgG and 1400 healthy controls in Guangzhou, South China. Human leukocyte antigen ( HLA ) sequencing was also utilized. Genotype model and haplotype, gene burden, and enrichment analyses were conducted. Results A significant region of the HLA composition is on chromosome 6, and great variation was observed in DQB1, DQA2 and DQA1 . HLA sequencing confirmed that the most significant allele was HLA‐DQB1*05:02 ( p < 0.01, odds ratio [OR] 3.73). The genotype model analysis revealed that HLA‐DQB1*05:02 was significantly associated with NMOSD in the additive effect model and dominant effect model ( p < 0.05). The proportion of haplotype “ HLA‐DQB1*05:02‐DRB1*15:01 ” was significantly greater in the NMOSD patients than the controls, at 8.42% and 1.23%, respectively ( p < 0.001, OR 7.39). The gene burden analysis demonstrated that loss‐of‐function mutations in NOP16 were more common in the NMOSD patients (11.84%) than the controls (5.71%; p < 0.001, OR 2.22). The IgG1‐G390R variant was significantly more common in NMOSD, and the rate of the T allele was 0.605 in patients and 0.345 in the controls ( p < 0.01, OR 2.92). The enrichment analysis indicated that most of the genetic factors were mainly correlated with nervous and immune processes. Conclusions Human leukocyte antigen is highly correlated with NMOSD. NOP16 and IgG1 ‐ G390R play important roles in disease susceptibility.
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