Child's Nervous System

, Volume 34, Issue 2, pp 277–284 | Cite as

Association of neural tube defects with gene polymorphisms in one-carbon metabolic pathway

  • Lirong Cao
  • Yizheng Wang
  • Ruiping Zhang
  • Liang Dong
  • Hualei Cui
  • Yulian Fang
  • Linsheng Zhao
  • Ouyan ShiEmail author
  • Chunquan CaiEmail author
Original Paper



Neural tube defects (NTDs) are common congenital malformations. In this study, we aimed to explore the association between single nucleotide polymorphisms (SNPs) related to one-carbon metabolism (OCM) and NTDs in Han population of Northern China.


A case-control study was conducted in 152 children with NTDs and 169 controls. Twenty-nine SNPs in five genes were genotyped by Sequenom MassARRAY technology, and haplotype analysis was done by Haploview4.2 software.


The allele frequency of rs3733890 in betaine-homocysteine methyltransferase (BHMT) gene was statistically different between NTDs and control groups (P = 0.041), and the children with A allele had higher risk for NTDs than G allele (OR = 1.408, 95%CI 1.013–1.956). In addition, there was a statistical difference in the allele and genotype frequencies of rs1051266 in reduced folate carrier1 (RFC1) gene between cases and controls (P = 0.013, 0.034), and the risk for NTDs was also higher in children with G allele and GG genotype, compared with A allele and AA genotype, respectively (OR = 1.492, 95%CI 1.089–2.044; OR = 2.020, 95%CI 1.081–3.780). The statistical significant difference was also found in allele frequency of rs1805087 in methionine synthetase (MTR) gene between cases and controls (P = 0.031), and the children with G allele were associated with an increased NTDs risk, compared with A allele (OR = 1.664, 95%CI 1.045–2.647). Meanwhile, haplotype analysis showed C-A-A-A haplotype of BHMT, and G-G-G-T haplotype of RFC1 was correlated with an increased risk of NTDs, but C-G-A-A haplotype of BHMT and G-G-C-A haplotype of MTR might decrease the risk of NTDs.


The BHMT gene rs3733890, RFC1 gene rs1051266 and MTR gene rs1805087 were associated with the occurrence of NTDs in Han population of Northern China. It was confirmed that the gene variation related to OCM was one of the susceptibility factors for NTDs.


Neural tube defects Polymorphisms One-carbon metabolism Susceptibility 



We are grateful to all the participants enrolled in this study. This study was supported by the National Key Basic Research Program of China (973 Program) (No. 2013CB945404); the Tianjin Research Program of Application Foundation and Advanced Technology (No. 14JCYBJC25000); the Key Project of Tianjin Health and Family Planning Commission Natural Science Foundation (No. 2015KRl2); the Key Project of Tianjin Health Care Professionals (No. 16KG166); and the National Natural Science Foundation of China (No. 81770612).

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were approved by the Medical Ethics Committee of Tianjin Children’s Hospital.

Research involving human participants and animals

This article did not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in this study.

Data availability

The datasets during and analyzed during the current study could be available from the corresponding author on reasonable request.


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Lirong Cao
    • 1
  • Yizheng Wang
    • 1
  • Ruiping Zhang
    • 1
  • Liang Dong
    • 2
  • Hualei Cui
    • 2
  • Yulian Fang
    • 3
  • Linsheng Zhao
    • 4
  • Ouyan Shi
    • 5
    Email author
  • Chunquan Cai
    • 6
    Email author
  1. 1.Graduate college of Tianjin Medical UniversityTianjinChina
  2. 2.Department of surgeryTianjin Children’s HospitalTianjinChina
  3. 3.Institute of pediatricTianjin Children’s HospitalTianjinChina
  4. 4.Department of pathologyTianjin Children’s HospitalTianjinChina
  5. 5.School of Basic Medical SciencesTianjin Medical UniversityTianjinChina
  6. 6.Department of neurosurgeryTianjin Children’s HospitalTianjinChina

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