Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Department of Basic Research, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Mult Scler Relat Disord. 2020 Jan;37:101438. doi: 10.1016/j.msard.2019.101438. Epub 2019 Oct 9.
X chromosome-linked interleukin-1 receptor-associated kinase (IRAK1) polymorphisms have been demonstrated to be associated with the risks of several autoimmune diseases, such as systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, and autoimmune thyroid diseases. However, no studies have investigated the association of IRAK1 polymorphisms with neuromyelitis optica spectrum disorder (NMOSD). This case-control study was performed to determine the correlation between IRAK1 polymorphisms and the risk of NMOSD.
Two single nucleotide polymorphisms (SNPs) rs1059703G>A and rs3027898C>A of IRAK1 were selected and genotyped using SNPscan in a Chinese cohort, including 332 patients with NMOSD and 520 healthy controls. Chi-square tests and logistic regression analyses were used to determine the associations between IRAK1 polymorphisms and the risk of NMOSD.
Patients with NMOSD showed a lower frequency of the minor allele A of rs1059703 than did controls (Odds ratio [OR] = 0.68; 95% confidence intervals [CI], 0.52-0.88; P = 0.007). Compared with wild genotype GG of rs1059703, homozygous mutation AA and heterozygous mutation GA were significantly associated with the decreased risk of NMOSD after adjusting for sex and age (adjusted OR = 0.64; 95%CI, 0.49-0.84; P = 0.002). Similar associations were also observed for IRAK1 rs3027898C>A. Stratification analysis according to sex revealed that the significantly different allele distributions of the two SNPs were mainly found in females. However, IRAK1 polymorphisms were not correlated with aquaporin-4-IgG, onset symptoms, or age at onset.
This study is first to demonstrate that X-chromosome-linked IRAK1 polymorphisms are associated with the risk of NMOSD and provide novel insights into the underlying mechanisms of this disease. Further studies are needed to elucidate the function of IRAK1 variants in the pathogenesis of NMOSD and the underlying molecular mechanisms.
X 染色体连锁的白细胞介素-1 受体相关激酶（IRAK1）多态性已被证明与多种自身免疫性疾病的风险相关，如系统性红斑狼疮、系统性硬化症、类风湿关节炎和自身免疫性甲状腺疾病。然而，尚无研究探讨 IRAK1 多态性与视神经脊髓炎谱系疾病（NMOSD）之间的关联。本病例对照研究旨在确定 IRAK1 多态性与 NMOSD 风险之间的相关性。
选择 IRAK1 的两个单核苷酸多态性（SNP）rs1059703G>A 和 rs3027898C>A，并使用 SNPscan 在包括 332 名 NMOSD 患者和 520 名健康对照的中国队列中进行基因分型。卡方检验和 logistic 回归分析用于确定 IRAK1 多态性与 NMOSD 风险之间的关联。
NMOSD 患者的 rs1059703 次要等位基因 A 的频率低于对照组（优势比 [OR] = 0.68；95%置信区间 [CI]，0.52-0.88；P = 0.007）。与 rs1059703 的野生基因型 GG 相比，纯合突变 AA 和杂合突变 GA 与 NMOSD 风险降低显著相关，在调整性别和年龄后（调整 OR = 0.64；95%CI，0.49-0.84；P = 0.002）。IRAK1 rs3027898C>A 也观察到类似的关联。根据性别进行分层分析表明，这两个 SNP 的显著不同等位基因分布主要存在于女性中。然而，IRAK1 多态性与水通道蛋白-4-IgG、发病症状或发病年龄无关。
本研究首次表明 X 染色体连锁的 IRAK1 多态性与 NMOSD 的风险相关，并为该疾病的发病机制提供了新的见解。需要进一步的研究来阐明 IRAK1 变异在 NMOSD 发病机制中的作用及其潜在的分子机制。
