Potential sex-specific associations between MTHFR C677T polymorphism and thyroid autoantibodies in spontaneous abortion: A retrospective study in the Lingnan region of China.

The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and thyroid autoimmunity are established risk factors for spontaneous abortion (SA). We aimed to explore the relationship between these factors in both sexes within the SA cohort from the Lingnan region of China. This retrospective cross-sectional study enrolled 474 women and 235 men at Shenzhen Second People's Hospital from July 2019 to November 2022. Participants were divided into three genotype groups (CC, CT, TT). Levels of anti-thyroperoxidase (TPO-Ab), anti-thyroglobulin (Tg-Ab) antibodies, and homocysteine (HCY) were quantified. In women with SA, TT carriers exhibited significantly higher TPO-Ab (P = 0.005), Tg-Ab (P < 0.001), and HCY (P = 0.002) levels than CC and CT. Thyroid autoantibodies levels did not differ across MTHFR genotypes in male participants. Multivariate regression analysis within the SA cohort, adjusted for age, BMI, and HCY, identified the TT genotype as a possible risk factor for elevated maternal TPO-Ab (adjusted β: 244.8, 95% CI: 15.9-473.8, P = 0.0387) and Tg-Ab levels (adjusted β: 138.7, 95 % CI: 17.0-260.4, P = 0.0279), but a likely protective factor for paternal TPO-Ab (adjusted β: -482.4, 95 % CI: -722.7 - -242.2, P = 0.0012) and Tg-Ab (adjusted β: -26.0, 95 % CI: -37.0 - -15.0, P = 0.0010). TPO-Ab (P = 0.003) and Tg-Ab (P = 0.002) levels were significantly higher in female TT genotype carriers than males of the SA cohort. Our findings suggest a potential sex-specific association between MTHFR C677T genotypes and thyroid autoimmunity in SA from the Lingnan Region of China.