Department of Neurology, West China Hospital, Sichuan University, No. 28 Dianxin Nanjie Street, Chengdu, 610041, China.
Neuromolecular Med. 2017 Dec;19(4):493-500. doi: 10.1007/s12017-017-8463-9. Epub 2017 Aug 29.
STAT4 plays a crucial role in the functioning of the innate and adaptive immune cells and has been identified as a susceptibility gene in numerous autoimmune disorders. However, its association with neuromyelitis optica spectrum disorders (NMOSD) remains uncertain. Here, we performed a case-control study to determine whether STAT4 contributed to the risk of NMOSD. We tested five STAT4 SNPs in 233 patients with established NMOSD and 492 healthy controls. Chi-square tests and logistic regression analyses were performed with four genetic models, including allelic, additive, dominant, and recessive models, to identify associations with NMOSD. The results of multiple test comparisons were corrected using the Benjamini and Hochberg false discovery rate (FDR-BH). After correcting for multiple test comparisons, the minor alleles of four STAT4 SNPs exhibited significant association with increased risk of NMOSD (rs7574865 T, odds ratio [OR] = 1.66, 95% confidence interval [CI] 1.32-2.08, P = 0.000; rs10181656 G, OR = 1.62, 95% CI 1.29-2.03, P = 0.000; rs10168266 T, OR = 1.59, 95% CI 1.27-2.00, P = 0.001; and rs13426947 A, OR = 1.51, 95% CI 1.21-1.90, P = 0.004). Identical results were observed in the dominant, recessive, and additive models. In contrast, the G allele of rs7601754 displayed a protective effect against NMOSD (OR = 0.53, 95% CI 0.36-0.76, P = 0.006). Our study indicates that STAT4 polymorphisms are associated with the risk of NMOSD, which provides novel insights into the underlying mechanisms of this disease.
STAT4 在先天和适应性免疫细胞的功能中起着至关重要的作用，并且已被确定为许多自身免疫性疾病的易感基因。然而，其与视神经脊髓炎谱系疾病（NMOSD）的关联尚不确定。在这里，我们进行了病例对照研究，以确定 STAT4 是否会增加 NMOSD 的风险。我们在 233 名确诊的 NMOSD 患者和 492 名健康对照中测试了五个 STAT4 SNPs。使用包括等位基因、加性、显性和隐性模型在内的四种遗传模型进行卡方检验和逻辑回归分析，以确定与 NMOSD 的关联。使用 Benjamini 和 Hochberg 假发现率（FDR-BH）对多重测试比较的结果进行了校正。在进行多重测试比较校正后，四个 STAT4 SNPs 的次要等位基因与 NMOSD 风险增加显著相关（rs7574865 T，比值比[OR] = 1.66，95%置信区间[CI] 1.32-2.08，P = 0.000；rs10181656 G，OR = 1.62，95%CI 1.29-2.03，P = 0.000；rs10168266 T，OR = 1.59，95%CI 1.27-2.00，P = 0.001；rs13426947 A，OR = 1.51，95%CI 1.21-1.90，P = 0.004）。在显性、隐性和加性模型中观察到相同的结果。相比之下，rs7601754 的 G 等位基因对 NMOSD 具有保护作用（OR = 0.53，95%CI 0.36-0.76，P = 0.006）。我们的研究表明，STAT4 多态性与 NMOSD 的风险相关，这为该疾病的潜在机制提供了新的见解。
