Association between Maternal and Fetal MTHFR C677T and MTRR A66G Polymorphisms with the Risk of NTDs: A Systematic Review and Meta-Analysis Study

Background: Neural tube defects (NTDs) are classed as multifactorial birth defects of the brain and spinal cord that arise during embryonic development. Although the etiology is not well understood, NTDs are reported to be prevented by maternal folic acid supplementation before and during early pregnancy. Objectives: This meta-analysis study aimed to assess the association between fetal and maternal methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms with the risk of NTDs. Methods: The PubMed, Scopus, and Springer Link databases were searched (from March 2000 to November 2020) for the literature on the association between MTHFR C677T and MTRR A66G polymorphisms with the risk of NTDs. Results: In total, 33 studies were reviewed in the present study, and it was revealed that, unlike MTRR A66G polymorphism, MTHFR C677T was statistically associated with the risk of NTDs in the overall population. The results of subgroup analysis showed that the Indian subcontinent subgroup with maternal MTHFR C677T polymorphism and the European subgroup with fetal MTHFR C677T polymorphism was significantly susceptible to NTDs. Conclusion: The obtained results revealed that, unlike MTRR A66G, maternal and fetal MTHFR C677T polymorphisms were significantly associated with NTDs. Subgroup analysis also demonstrated that folic acid deprivation can be considered the main cause of MTHFR C677T polymorphism in some areas.