Association between C677T variant of methylene tetrahydrofolate reductase and hypospadias risk in Algeria
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...
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Hacettepe University Institute of Child Health
2025-07-01
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| Series: | The Turkish Journal of Pediatrics |
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| Online Access: | https://turkjpediatr.org/article/view/6049 |
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| author | Rania Laouar Djalila Chellat-Rezgoune Meroua Horchi Rayene Achou Brahim Djoudi Souhem Touabti Yacine Benhizia Karima Sifi |
| author_facet | Rania Laouar Djalila Chellat-Rezgoune Meroua Horchi Rayene Achou Brahim Djoudi Souhem Touabti Yacine Benhizia Karima Sifi |
| author_sort | Rania Laouar |
| collection | DOAJ |
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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.
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| format | Article |
| id | doaj-art-48eb4ee258364cd8bbceda8d018e91f3 |
| institution | DOAJ |
| issn | 0041-4301 2791-6421 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Hacettepe University Institute of Child Health |
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| series | The Turkish Journal of Pediatrics |
| spelling | doaj-art-48eb4ee258364cd8bbceda8d018e91f32025-08-20T03:08:59ZengHacettepe University Institute of Child HealthThe Turkish Journal of Pediatrics0041-43012791-64212025-07-0167310.24953/turkjpediatr.2025.6049Association between C677T variant of methylene tetrahydrofolate reductase and hypospadias risk in AlgeriaRania Laouar0https://orcid.org/0000-0002-4392-5156Djalila Chellat-Rezgoune1https://orcid.org/0000-0002-0161-0746Meroua Horchi2https://orcid.org/0009-0009-0467-9464Rayene Achou3https://orcid.org/0009-0004-0709-0130Brahim Djoudi4https://orcid.org/0000-0002-7924-2939Souhem Touabti5https://orcid.org/0000-0002-5497-0470Yacine Benhizia6https://orcid.org/0000-0003-3944-4971Karima Sifi7https://orcid.org/0009-0000-7132-5150Laboratory of Molecular and Cellular Biology, Department of Animal Biology, Faculty of Natural and Life Science, University of Mentouri Constantine 1, Constantine, AlgeriaLaboratory of Molecular and Cellular Biology, Department of Animal Biology, Faculty of Natural and Life Science, University of Mentouri Constantine 1, Constantine, AlgeriaLaboratory of Molecular and Cellular Biology, Department of Animal Biology, Faculty of Natural and Life Science, University of Mentouri Constantine 1, Constantine, AlgeriaLaboratory of Molecular and Cellular Biology, Department of Animal Biology, Faculty of Natural and Life Science, University of Mentouri Constantine 1, Constantine, AlgeriaLIRE Laboratory, Department of Biochemistry, University of Mentouri Constantine 1, Constantine, AlgeriaPediatric Urology Unit, C.H.U Sétif, Sétif, AlgeriaLaboratory of Molecular and Cellular Biology, Department of Microbiology, Faculty of Natural and Life Science, University of Mentouri Constantine 1, Constantine, AlgeriaLaboratory of Biology and Molecular Genetics, Faculty of Medicine, University of Constantine 3, Constantine, Algeria 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. https://turkjpediatr.org/article/view/6049hypospadiasMTHFRC677Trisk factorsfolic acidpolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) |
| spellingShingle | Rania Laouar Djalila Chellat-Rezgoune Meroua Horchi Rayene Achou Brahim Djoudi Souhem Touabti Yacine Benhizia Karima Sifi Association between C677T variant of methylene tetrahydrofolate reductase and hypospadias risk in Algeria The Turkish Journal of Pediatrics hypospadias MTHFR C677T risk factors folic acid polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) |
| title | Association between C677T variant of methylene tetrahydrofolate reductase and hypospadias risk in Algeria |
| title_full | Association between C677T variant of methylene tetrahydrofolate reductase and hypospadias risk in Algeria |
| title_fullStr | Association between C677T variant of methylene tetrahydrofolate reductase and hypospadias risk in Algeria |
| title_full_unstemmed | Association between C677T variant of methylene tetrahydrofolate reductase and hypospadias risk in Algeria |
| title_short | Association between C677T variant of methylene tetrahydrofolate reductase and hypospadias risk in Algeria |
| title_sort | association between c677t variant of methylene tetrahydrofolate reductase and hypospadias risk in algeria |
| topic | hypospadias MTHFR C677T risk factors folic acid polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) |
| url | https://turkjpediatr.org/article/view/6049 |
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