Abstract
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 corr=0.000; rs10181656 G, OR=1.62, 95% CI 1.29-2.03, P corr=0.000; rs10168266 T, OR=1.59, 95% CI 1.27-2.00, P corr=0.001; and rs13426947 A, OR=1.51, 95% CI 1.21-1.90, P corr=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 corr=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.
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