Association between MTHFD1 polymorphisms and neural tube defect susceptibility

Area of Science:

• Genetics
• Neonatal Health
• Folate Metabolism

Background:

• Neural tube defects (NTDs) are common congenital anomalies with complex origins.
• Periconceptional folic acid is hypothesized to prevent NTD risk.
• The MTHFD1 gene plays a crucial role in folate metabolism and is associated with NTD risk.

Purpose of the Study:

• To investigate the association between MTHFD1 gene polymorphisms and NTD susceptibility.
• To evaluate three specific single-nucleotide polymorphisms (SNPs) in the MTHFD1 gene: 401A>G, 2305C>T, and 1958G>A.

Main Methods:

• A case-control study involving 222 neonates (122 with NTD, 100 healthy controls).
• Genotyping of MTHFD1 SNPs (401A>G, 2305C>T, 1958G>A) using the SNapShot method.
• Statistical analysis including Mann-Whitney test, ANOVA, chi-square test, and a meta-analysis for the 1958G>A variant.

Main Results:

• The MTHFD1 1958G>A polymorphism (specifically the AA genotype) showed a significant association with increased NTD risk in the studied population.
• No statistically significant association was found for the 401A>G and 2305C>T SNPs with NTD risk.
• A meta-analysis suggested that the 1958G>A variant may not be a genetic risk factor in the Caucasian population.

Conclusions:

• The MTHFD1 1958G>A polymorphism is significantly associated with NTD susceptibility in the Chinese population.
• AA homozygote carriers of the 1958G>A variant have a higher likelihood of developing NTD.
• Further research is required to validate the risk effect and functional impact of this MTHFD1 polymorphism.