Role of parental folate pathway single nucleotide polymorphisms in altering the susceptibility to neural tube defects in South India

Abstract

Aim: To investigate the role of four parental folate pathway single nucleotide polymorphisms (SNPs) i.e., methylene tetrahydrofolate reductase (MTHFR) 677C>T, MTHFR 1298A>C, methionine synthase reductase (MTRR) 66A>G and glutamate carboxypeptidase (GCP) II 1561C>T on susceptibility to neural tube defects (NTDs) in 50 couples with NTD offspring and 80 couples with normal pregnancy outcome.

Results: Maternal MTHFR 677C→T (odds ratio (OR): 2.69, 95% confidence interval (CI): 1.35–5.34) and parental GCP II 1561C→T (maternal: OR: 1.89, 95% CI: 1.12–3.21 and paternal: OR: 3.23, 95% CI: 1.76–5.93) were found to be risk factors for a NTD. Both paternal and maternal GCP II T-variant alleles were found to interact with MTHFR 677T- and MTRR G-variant alleles in increasing the risk for NTD. Segregation of data based on type of defect revealed an association between maternal 677T-allele and meningomyelocele (OR: 9.00, 95% CI: 3.77–21.55, P<0.0001) and an association between parental GCP II 1561T-allele and anencephaly (maternal: OR: 2.25, 95% CI: 1.12–4.50, P<0.05 and paternal: OR: 4.26, 95% CI: 2.01–9.09, P<0.001).

Conclusions: Maternal MTHFR C677T and parental GCP II C1561T polymorphisms are associated with increased risk for NTDs. Apart from individual genetic effects, epistatic interactions were also observed.