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



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).



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.
Naushad
Shaik Mohammad
SM
Division of Diagnostic, Center for DNA Fingerprinting and Diagnostics, Hyderabad, India. naushadsm@gmail.com
Devi
Akella Radha Rama
AR
D000328:Adult; D002268:Carboxypeptidases / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D005492:Folic Acid / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009436:Neural Tube Defects / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D002268:Carboxypeptidases; C026134:glutamate carboxypeptidase