Evaluation of genetic heterogeneity in glutamate carboxypeptidase II (H475Y) and reduced folate carrier (SLC19A1) gene variants increased risk factor for the development of neural tube defects in eastern region of India

In humans, neural tube failure to close during the 4th week of gestation leads to the development of severe congenital malformations of the central nervous system because of an error in maternal folate metabolism associated gene variants. The frequency of genotypic variants of GCP II (H475Y) and folate carrier RFCI (SLC19A1) gene polymorphism (80 G →A) were evaluated as potential candidate gene(s) and also assess their clinical association to increase “risk” in neural tube defects (NTDs). In the present study, blood samples (0.5 ml) were collected from NTD cases, mother and their respective controls and genomic DNA was isolated to evaluate the impact of GCP II and RFCI genotypic variants as risk factor using polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP) analysis. Significant differences (p<0.05) were observed between case mothers and control for GCP II genotype using Fischer’s exact two tailed probability test. The odd ratio was calculated to determine the risk factors at 95% C.I. (1.56-87.60), which seems to be very high, suggesting significant involvement of GCP II gene in the development of NTDs. The significant (p = 0.03) risk factor was also calculated (OR=4.85: 95%, C.I. 1.33-17.36) for RFCI gene between heterozygote (GA) and homozygote (AA) mothers having NTDs child. The present finding strongly suggests that genotype variants of GCPII and RFCI gene, in heterozygous condition, are responsible for increasing as independent risk factor for the development of NTDs like meningomyelocele (MMC) susceptibility in this region.