ABSTRACT
Objective To investigate the contribution of single nucleotide polymorphisms (SNP)variation in folate metabolism pathway genes and its interaction with environmental risk factors to the etiology of NTD. Methods In 275 families from central China, a total of 278 aborted fetal tissues or blood samples were collected from NTD individuals, 478 maternal and/or paternal blood samples were also obtained as controls. Folate supplementation, maternal diabetes mellitus and medication before pregnancy and during the first trimester of pregnancy were investigated. SNP analyses of all samples were performed by CEQ 8800. Case-parent control study and transmission/disequilibrium tests (TDT) were performed according to environmental cofactors stratification to evaluated 28 SNP in 12 folate pathway genes associated with human NTD. Results Only gene MTHFR rs1801133 was significantly associated with NTD, and synergistic effects of environmental risk factors (no folate supplementation and maternal diabetes) were shown on the occurrence of NTD. Linkage disequilibrium between BHMT rs3733890 and NTD existed in case of no folate supplementation,whereas the genotype alone did not contribute to the etiology of NTD. Other SNP were not significantly associated with NTD. Conclusions MTHFR rs1801133 is a risk factor of NTD, but BHMT rs3733890 is not an independent risk factor. Further investigations in folate and methionine cycle genes are requird in larger scale to enclose the interactions between gene and gene, or gene and environmental factors.