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. 2025 Jan-Feb;39(1):172-179.
doi: 10.21873/invivo.13815.

Impacts of Methylenetetrahydrofolate Reductase Genotypes on Hallux Valgus

Chien-Chung Kuo #  1   2 , Chun-Hao Tsai #  1   3 , Fu-Kai Chuang #  4   5 , Yun-Chi Wang  3   6 , Mei-Chin Mong  7 , Ya-Chen Yang  7 , Hou-Yu Shih  3   6 , Shih-Wei Hsu  3   6 , Wen-Shin Chang  3   6 , DA-Tian Bau  8   6   9 , Chia-Wen Tsai  8   6
Affiliations

Impacts of Methylenetetrahydrofolate Reductase Genotypes on Hallux Valgus

Chien-Chung Kuo et al. In Vivo. 2025 Jan-Feb.

Abstract

Background/aim: Hallux valgus (HV) is the most common deformity of the forefoot. Although HV has been strongly associated with a family history, its genetic underpinnings remain unclear. Few studies have examined the relationship between folic acid metabolism, which is critical in normal bone development, and HV. The study aimed to investigate the contribution of methylenetetrahydrofolate reductase (MTHFR) genotypes to the risk of HV.

Materials and methods: The MTHFR rs1801133 and rs1801131 genotypes were analyzed in 150 patients with HV and 600 controls without HV, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results: The results highlighted a significant difference in the genotypic frequency distributions of MTHFR rs1801133 between the HV cases and non-HV controls (p for trend=0.0024). Specifically, individuals with the homozygous TT genotype at MTHFR rs1801133 exhibited a 2.57-fold increased risk of HV (95% confidence interval=1.49-4.42, p=0.0009). However, those with the CT genotype did not show an elevated risk. Stratified analysis showed no correlation between MTHFR rs1801133 genotypic distributions and different age groups (below or above 51 years) or sex (both p>0.05). Furthermore, no associations were identified between MTHFR rs1801133 and height, weight, or body mass index in relation to HV risk.

Conclusion: The TT genotype of MTHFR rs1801133 is associated with an increased risk of HV. Subgrouping HV patients based on their MTHFR genotypes and related comorbidities, such as rheumatoid arthritis, may offer a new approach to diagnosis.

Keywords: Genotype; Taiwan; hallux valgus; methylenetetrahydrofolate reductase (MTHFR); polymorphism.

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Conflict of interest statement

The Authors declare no conflicts of interest regarding this study.

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