Turk J Pediatr. 2025 Jul 6;67(3):398-409. doi: 10.24953/turkjpediatr.2025.6049.
ABSTRACT
BACKGROUND: Hypospadias, a congenital condition characterized by the urethral opening being on the underside of the penis, has received limited attention in its association with the MTHFR C677T variant. Given the crucial role of folate metabolism in embryonic development, and the involvement of the MTHFR C677T polymorphism in folate metabolism, this study aims to investigate whether this variant contributes to the risk of hypospadias in an Algerian population.
METHODS: This case-control study included 105 patients with hypospadias and 125 controls. Genotyping of the MTHFR gene C677T variant was performed using polymerase chain reaction-restriction fragment length polymorphism.
RESULTS: A statistically significant difference in the genotype distribution of the MTHFR C677T variant between patients with hypospadias and controls was revealed. The significance was observed in the codominant genetic model CT vs. CC (p=0.034, odds ratio [OR]: 1.89, 95% CI: 1.04-3.44) and TT vs. CC (p=0.042, OR: 2.15, 95% CI: 1.02-4.53), as well as in the dominant model CC vs. CT+TT (p=0.010, OR: 1.98, 95% CI: 1.17-3.35). Maternal periconceptional folic acid supplement intake showed a significant association with the anatomical types of hypospadias in relation to the MTHFR C677T genotypes when folic acid was taken (p=0.006). Furthermore, a significant association was observed with the TT genotype in isolated hypospadias cases (p=0.038, OR=3.47, 95% CI: 1.03-11.68), suggesting a potential role of folic acid in modifying hypospadias risk. Multiple logistic regression analysis identified intrauterine growth restriction, gestational hypertension, residency, and the MTHFR C677T variant as independent potential risk factors for hypospadias development (p-values: 0.030, 0.016, 0.040, and 0.045, respectively).
CONCLUSIONS: This study reports, for the first time, an association between the MTHFR gene C677T variant and hypospadias in the Algerian population. The findings suggest a strong association between the MTHFR C677T variant and susceptibility to hypospadias. Identified risk factors such as intrauterine growth restriction, gestational hypertension, rural residency, and the MTHFR C677T variant contribute valuable insights into the multifaceted etiology of hypospadias in this population.
PMID:40674756 | DOI:10.24953/turkjpediatr.2025.6049
