Association of c.1298A>C Variation in Methylenetetrahydrofolate reductase Gene with Neural Tube Defects: Case-Control study in Syrian population


Neural tube defects (NTDs) are the most common multifactorial congenital disorders worldwide. Some genetic variations in Methylenetetrahydrofolate reductase (MTHFR) gene were shown to be associated with NTDs. In this case-control study, we aimed to investigate the effect of c.1298A>C variation on NTDs risk in a cohort of Syrian population. The study consisted of 262 individuals distributed into two groups; the first group involved 72 isolated NTDs-cases and 86 healthy controls, the second group included 30 mothers of NTDs-offspring as cases and 74 mothers with no previous family history of NTDs or any other birth defects, as controls. No significant association was found between the c.1298A>C variant and the risk of NTDs. However, a significant association was found in both over-dominant and heterozygous co-dominant genetic models, in maternal c.1298A>C variation suggesting a risk factor for having NTDs by more than 2-fold. Furthermore, our data point out to a possible interaction between maternal-fetal genotypes and nutritional factors in inducing NTDs. Our findings strongly emphasize the leading role of maternal genotype in determining the pregnancy outcomes. Awareness is needed in our society to the importance of adequate diet and taking nutritional supplements before and during pregnancy. This is the first study on NTDs and their etiology in Syria, further studies are needed.