Abstract: Objective To investigate the relationship between single nucleotide polymorphisms (SNPs) of betaine homocysteine methyltransferase (BHMT) and reduced folate carrier 1 (RFC1, SLC19A1) genes and susceptibility to neural tube defects (NTDs) in children of Han population in northern China. Methods A total of 152 NTDs patients, and 169 controls were used in this study. Sequenom Mass-ARRAY was used to genotype 9 SNPs in 2 genes, and Haploview 4.2 software was used for Haplotype analysis. Results The allele frequency of rs3733890 in BHMT was significantly correlated with the incidence of NTDs, and the children with A allele were at higher risk of NTDs compared with those with G allele (OR=1.408,95%CI: 1.013-1.956). The distribution of allele and genotype frequencies of rs1051266 in RFC1 was significantly associated with the incidence of NTDs, and the children with G allele and GG genotype were associated with higher risk of NTDs compared with those with A allele and AA genotype (OR=1.492, 95%CI: 1.089-2.044; OR=2.020, 95%CI: 1.081-3.780).The allele frequency of rs3788200 in RFC1 was significantly correlated with the incidence of NTDs, and the children with G allele were at higher risk of NTDs than those with A allele (OR=1.368, 95%CI: 1.002-1.868). Meanwhile, Haplotype analysis showed that C-A-A-A haplotype (rs567754-rs3733890-rs558133-rs585800) of BHMT and G-G-G-T haplotype(rs1051296-rs3788200-rs1051266-rs4819130) of RFC1 were associated with the increased risk of NTDs, but C-G-A-A haplotype of BHMT gene was associated with the decreased risk of NTDs. Conclusion The rs3733890 of BHMT gene,rs1051266 and rs3788200 of RFC1 gene are associated with susceptibility to NTDs in children of Han population in northern China.

Key words: neural tube defects, polymorphism, single nucleotide, folic acid, genetic predisposition to disease, child, Han nationality, homocysteine, BHMT, RFC1