title: Association between MTHFD1 G1958A polymorphism and neural tube defects susceptibility: a meta-analysis.
abstract: OBJECTIVE
  The methylenetetrahydrofolate dehydrogenase (MTHFD1) gene, as one of the key genes involved in the folate pathway, has been reported to play a critical role in the pathogenesis of neural tube defects (NTDs). However, the results of published studies are contradictory and inconclusive. Thus, this meta-analysis aimed to evaluate the effect of the common polymorphism in the MTHFD1 gene, the G1958A (R653Q, dbSNP ID: rs2236225) variant, on the risk of NTDs in all eligible studies.
  
  
  METHODS
  Relevant literature published before January 3, 2014 was retrieved from the MEDLINE, EMBASE, Cochrane Library, and CBM databases. Pooled crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated to evaluate the association between the MTHFD1 G1958A polymorphism and NTDs risk.
  
  
  RESULTS
  We performed a meta-analysis of nine studies with a total of 4,302 NTDs patients and 4,238 healthy controls. Our results demonstrated a significant correlation between the MTHFD1 G1958A polymorphism and NTDs in an overall meta-analysis. For family-based studies, the study subjects were classified as NTD cases, mothers with NTDs offspring, and fathers with NTDs offspring. We found no association between any of the fathers' genotypes and NTDs, whereas there was a clear excess of the 1958A allele in the mothers of children with NTDs compared with controls individuals.
  
  
  CONCLUSIONS
  In summary, our meta-analysis strongly suggests that the MTHFD1 G1958A polymorphism might be associated with maternal risk for NTDs in Caucasian populations. However, the evidence of this association should be interpreted with caution due to the selective nature of publication of genetic association studies.
authors: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China; Department of Neurosurgery, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Jianxin
authors: J
authors: Jiang
authors: Department of Neurosurgery, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Yanfei
authors: Y
authors: Zhang
authors: Department of Neurosurgery, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Liang
authors: L
authors: Wei
authors: Department of Neurosurgery, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Zhiyang
authors: Z
authors: Sun
authors: Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China; Department of Neurosurgery, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Zhongmin
authors: Z
authors: Liu
mesh_terms: D000483:Alleles; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics*; D015778:Minor Histocompatibility Antigens; D009436:Neural Tube Defects / Q000201:enzymology* / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
chemical_list: D015778:Minor Histocompatibility Antigens; C539735:MTHFD1 protein, human; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP)