Background: Worldwide, Neural tube defects (NTDs) are considered as major clinical problems imposing a huge socio-economic burden for both affected individuals and their families. In India, the prevalence of Neural tube defects is significantly high. This study aims to evaluate the association between genetic defects in folate metabolism pathway genes, mainly: Folate hydrolase 1 (FOLH1), Dihydrofolate reductase (DHFR) and Methylenetetrahydrofolate reductase (MTHFR) and neural tube defects from eastern India.
Methods: We enrolled 62 consecutive mothers with NTDs foetuses as cases and their corresponding age matched 73 mothers with healthy babies as controls (genetic power has been calculated). Four single nucleotide polymorphisms (FOLH1: rs202676, DHFR: rs70991108, MTHFR: rs1801133 and rs1801131) have been amplified by polymerase chain reaction (PCR) and sequenced. Statistical analysis has been undertaken to find out association with NTDs.
Results: Genotype and allele frequency analysis of these SNPs revealed that, rs1801133 (p.Ala222Val) was significantly associated with NTDs risk (p value = 0.028; odds ratio-2.31; 95% CI 1.08-4.93), whereas rs202676 (p.Tyr60His) showed protective role (p value = 0.0066; odds ratio-0.11; 95% CI 0.01-0.86). Serum homocysteine (Hcy) concentration was respectively higher in subjects carrying 222Ala/Val and 222Val/Val alleles (p value = 0.009; p value ≤ 0.0001).
Conclusion: In conclusion, it can be stated that, rs1801133 was associated with neural tube defects risk in patients from the eastern part of India and it might be counted as a molecular marker for evaluating the susceptibility of NTDs.
Keywords: DHFR; FOLH1; Folate; MTHFR; Neural tube defects; and Homocysteine.
© 2018 Wiley Periodicals, Inc.