MSH5 Gene Polymorphisms Are Associated with Hashimoto’s Thyroiditis Susceptibility in a Chinese Han Population

Background This study investigated associations between MSH5 polymorphisms and autoimmune thyroid disease (AITD) susceptibility.Methods We genotyped rs409558 and rs707939 in 943 patients with AITD, including 591 with Graves’ disease (GD) and 352 with Hashimoto’s thyroiditis (HT), and 488 controls. Genetic associations were assessed before and after adjustment for age and sex. MAX3 testing with Bonferroni correction and haplotype analysis were performed. Linkage disequilibrium was assessed in healthy controls.Results rs409558 was not associated with AITD or its subtypes. The unadjusted association between rs707939 and overall AITD was attenuated after adjustment. Associations with HT remained significant after adjustment (allele model: OR = 1.28, p = .032; dominant model: OR = 1.84, p = .016). MAX3 testing favored the additive model for HT, with significance retained after Bonferroni correction. The variants shared a haplotype block, with high D′ (0.96) but low r2 (0.10), indicating limited allelic correlation. The TA haplotype was associated with reduced HT risk (OR = 0.64, 95% CI: 0.51–0.81, p < .001).Conclusion MSH5 rs707939 and the TA haplotype were associated with HT susceptibility. Further studies are needed to validate these associations and clarify their functional basis.