天津医药

天津医药 ›› 2018, Vol. 46 ›› Issue (9): 942-947.doi: 10.11958/20180345

• 临床研究 • 上一篇    下一篇

BHMT和RFC1多态性与中国北方汉族儿童神经管缺陷的易感性研究

王懿征，舒剑波，方玉莲，蔡春泉   

  1. 1天津医科大学研究生院（邮编300070）；2天津市儿童医院儿科研究所，3神经外科
  • 收稿日期:2018-03-08 修回日期:2018-05-31 出版日期:2018-09-15 发布日期:2018-10-10
  • 通讯作者: 蔡春泉 E-mail:15122656313@126.com

BHMT and RFC1 polymorphisms and susceptibility to neural tube defects in children of Han population in northern China

WANG Yi-zheng, SHU Jian-bo, FANG Yu-lian, CAI Chun-quan   

  1. 1 Graduate College of Tianjin Medical University, Tianjin 300070, China; 2 Institute of Pediatrics,3 Department of Neurosurgery, Tianjin Children’s Hospital
  • Received:2018-03-08 Revised:2018-05-31 Published:2018-09-15 Online:2018-10-10
  • Contact: Chun-Quan CAI E-mail:15122656313@126.com

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摘要： 目的 研究中国北方汉族儿童中甜菜碱同型半胱氨酸甲基转移酶基因（BHMT）和还原叶酸载体1基因（RFC1，又称SLC19A1）的单核苷酸多态性（SNPs）与神经管缺陷（NTDs）易感性的关系。方法 以中国北方汉族152例NTDs患儿和169例正常对照为研究对象，采用Sequenom Mass-ARRAY分型技术对BHMT和RFC1两个基因的9个SNPs 位点进行基因分型，Haploview4.2 软件进行单体型分析。结果 BHMT 基因 rs3733890 位点等位基因频率与NTDs 的发病存在显著关联，且携带 A 等位基因儿童发生 NTDs 风险高于 G 等位基因的儿童（OR=1.408，95%CI： 1.013～1.956）；RFC1基因rs1051266位点等位基因和基因型频率分布与NTDs的发病存在显著关联，且携带G等位基因和 GG 基因型的儿童患 NTDs 风险分别高于 A 等位基因和 AA 基因型儿童（OR=1.492，95%CI：1.089～2.044；OR=2.020，95%CI：1.081～3.780）；RFC1基因rs3788200位点等位基因频率与NTDs发病存在显著关联，携带G等位基因的儿童患NTDs风险高于携带A等位基因儿童（OR=1.368，95%CI：1.002~1.868）。同时，单体型分析结果显示BHMT基因单体型C-A-A-A（rs567754-rs3733890-rs558133-rs585800）和RFC1基因单体型G-G-G-T（rs1051296-rs3788200-rs1051266-rs4819130）可使 NTDs 发病风险增加，而 BHMT 基因单体型 C-G-A-A 可使 NTDs 发病风险降低。结论BHMT基因rs3733890和RFC1基因rs1051266、rs3788200多态性与中国北方汉族儿童NTDs的易感性相关。

关键词: 神经管缺损；多态性, 单核苷酸；叶酸；疾病遗传易感性；儿童；汉族；同型半胱氨酸；BHMT；RFC1

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