Correlation analysis of MTHFD1 gene polymorphisms and neural tube defects in Han population of Northern China

Abstract Background Neural tube defects (NTDs) is a common birth defects worldwide. The methylenetetrahydrofolate dehydrogenase1 (MTHFD1) gene has been proved to play an important role in folate metabolism, which was strongly associated with the increased NTDs risk. The study is aimed to explore the correlation of single nucleotide polymorphisms (SNPs) in MTHFD1 gene with NTDs susceptibility. Methods A case-control study was conducted on children who included 152 NTDs patients and 169 healthy controls. Tag-SNPs were identified in HapMap database. Then, we investigated the association between NTDs and four selected tag-SNPs in MTHFD1 gene: rs1950902, rs2236225, rs2236224, rs11849530. We also performed a meta-analysis based on previous published studies to further evaluate the association. Results The results indicated that rs2236225 polymorphism displayed a significant association with NTDs risk (AA vs. GG: OR = 2.862, 95%CI = 1.022ཞ8.015; GA + AA vs. GG: OR = 1.619, 95%CI = 1.040ཞ2.520; A vs. G: OR = 1.500, 95%CI = 1.061ཞ2.120). In addition, rs2236224 polymorphism was correlated with increased NTDs risk (TT vs. CC: OR = 2.559, 95%CI = 1.128ཞ5.804; CT + TT vs. CC; OR = 1.631, 95%CI = 1.041ཞ2.556; T vs C: OR = 1.489, 95%CI = 1.072ཞ2.068). Further analysis showed the harmful effect of rs2236225 polymorphism was further supported by the result of meta-analysis. Meanwhile, haplotype analysis results showed that A-A and T-A haplotypes were correlated with increased NTDs risk, but C-A haplotype might decrease NTDs risk. Conclusions The results indicated that rs2236225 and rs2236224 polymorphisms of MTHFD1 gene were significantly associated with NTDs susceptibility in Han population of Northern China.