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Child's Nervous System

, Volume 34, Issue 4, pp 725–729 | Cite as

Association of main folate metabolic pathway gene polymorphisms with neural tube defects in Han population of Northern China

  • Yulian Fang
  • Ruiping Zhang
  • Xiufang Zhi
  • Linsheng Zhao
  • Lirong Cao
  • Yizheng Wang
  • Chunquan Cai
Original Paper

Abstract

Purpose

Neural tube defects (NTDs) are one of the most prevalent and the most severe congenital malformations worldwide. Studies have confirmed that folic acid supplementation could effectively reduce NTDs risk, but the genetic mechanism remains unclear. In this study, we explored association of single nucleotide polymorphisms (SNP) within folate metabolic pathway genes with NTDs in Han population of Northern China.

Methods

We performed a case-control study to compare genotype and allele distributions of SNPs in 152 patients with NTDs and 169 controls. A total of 16 SNPs within five genes were genotyped by the Sequenom MassARRAY assay.

Results

Our results indicated that three SNPs associated significantly with NTDs (P<0.05). For rs2236225 within MTHFD1, children with allele A or genotype AA had a high NTDs risk (OR=1.500, 95%CI=1.061~2.120; OR=2.862, 95%CI=1.022~8.015, respectively). For rs1801133 within MTHFR, NTDs risk markedly increased in patients with allele T or genotype TT (OR=1.552, 95%CI=1.130~2.131; OR=2.344, 95%CI=1.233~4.457, respectively). For rs1801394 within MTRR, children carrying allele G and genotype GG had a higher NTDs risk (OR=1.533, 95%CI=1.102~2.188; OR=2.355, 95%CI=1.044~5.312, respectively).

Conclusions

Our results suggest that rs2236225 of MTHFD1 gene, rs1801133 of MTHFR gene and rs1801394 of MTRR gene were associated with NTDs in Han population of Northern China.

Keywords

Neural tube defects Polymorphisms Folate metabolism Susceptibility 

Notes

Acknowledgments

We are grateful to all the families for their NTDs-affected children enrolled in this study. We also extend our thanks to the staff of Tianjin Children’s Hospital for their cooperation and support in the collection of samples.

Funding information

This research was supported by the National 973 Program on Population and Health (no. 2013CB945404), the Natural Science Foundation of Tianjin City of China (no. 14JCYBJC25000), the Ministry of Science and Technology of P.R. China, and the Project of Tianjin Health Care Professionals (no. 15KR12), the Key Project of Tianjin Health Care Professionals (no.16KG166), and the National Natural Science of Foundation of China (no. 81770612).

Compliance with ethical standards

This study was approved by the Ethics Committee of Tianjin Children’s Hospital and written informed consent for the use of clinical data and blood samples was signed by all participants.

Conflict of interest

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

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Yulian Fang
    • 1
  • Ruiping Zhang
    • 2
  • Xiufang Zhi
    • 2
  • Linsheng Zhao
    • 3
  • Lirong Cao
    • 2
  • Yizheng Wang
    • 2
  • Chunquan Cai
    • 4
  1. 1.Institute of PediatricsTianjin Children’s HospitalTianjinChina
  2. 2.Graduate College of Tianjin Medical UniversityTianjinChina
  3. 3.Department of PathologyTianjin Children’s HospitalTianjinChina
  4. 4.Department of NeurosurgeryTianjin Children’s HospitalTianjinChina

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