ArticleInternational journal of women's health2026
Association Between MTHFR Gene Polymorphisms and Subclinical Hypothyroidism in Early Pregnancy: A Retrospective Case-Control Study.
Article in International journal of women's health, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objective: To investigate the association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and subclinical hypothyroidism (SCH) in early pregnancy. Methods: This retrospective case-control study included 100 pregnant women diagnosed with SCH and 300 pregnant women with normal thyroid function who attended the Affiliated Hospital of Jiangnan University between June 2021 and December 2024. MTHFR C677T and A1298C polymorphisms were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Thyroid function indicators, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were measured. Genotype and allele distributions were compared, and dominant, recessive, and additive genetic models were analyzed. Multivariate logistic regression analysis was performed to identify factors associated with SCH. Results: The proportions of abnormal pre-pregnancy body mass index (BMI) and anemia history were significantly higher in the SCH group than in the control group (P<0.05). Genotype distributions of both MTHFR loci conformed to Hardy-Weinberg equilibrium. Significant differences were observed in genotype and allele distributions of the C677T locus between the two groups (P<0.05), whereas no significant differences were found for the A1298C locus (P>0.05). Significant associations were observed under dominant, recessive, and additive models for the C677T polymorphism (P<0.05). Pregnant women with the TT genotype showed higher TSH levels than those with the CC and CT genotypes (P<0.05). Multivariate logistic regression analysis identified the C677T T allele, abnormal pre-pregnancy BMI, and anemia history as factors associated with SCH (P<0.05). Conclusion: The MTHFR C677T polymorphism is associated with SCH in early pregnancy, whereas no significant association was observed for the A1298C polymorphism. Abnormal pre-pregnancy BMI and anemia history may also be associated with increased SCH risk. Further prospective multicenter studies are required to validate these findings.
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