Edith Movazeb1 , Carlos Flores1, Rigoberto Ríos1, Sol Ríos1, Luis Fu1, Jorge D Mendez-Rios1,2
https://doi.org/10.37980/im.journal.ggcl.en.20252599
Introduction: The MTHFR gene, located at 1p36.22, is involved in the conversion of homocysteine to methionine via folate metabolism, which is essential for DNA, RNA, and protein synthesis. Variants such as C677T and A1298C have been associated with neural tube defects, thrombosis, schizophrenia, and homocystinuria due to MTHFR deficiency—an autosomal recessive condition characterized by toxic accumulation of homocysteine. Methodology: A systematic search was conducted using the OMIM database. Tasks were distributed among team members to ensure validated content, collaborative writing, and consistent structure.
Results: A total of 113 studies were identified: 11 case-control studies, 9 genetic association studies, 8 meta-analyses, 4 letters to the editor, 4 negative association studies, and only 2 cohort and 2 genomic studies. Mutations affect the activity of the MTHFR enzyme, leading to multisystem dysfunctions. Homocystinuria presents neurological, ocular, skeletal, and vascular manifestations. No conclusive evidence of haploinsufficiency or triplosensitivity was found according to ClinGen. Discussion: The literature shows sustained interest in MTHFR, although results are mixed. Functional variants may contribute to complex disorders, but epigenetic, environmental, and gene-gene interactions also play a role. The limited number of longitudinal and molecular studies restricts a comprehensive understanding of the gene. Conclusion: MTHFR is a key genetic marker in personalized medicine. The predominance of observational studies highlights the need to diversify methodological approaches and functionally validate its clinical role, encouraging genetic screening and preventive interventions with folate.
Keywords:
genes, evidence, clinic, genomics