title: Genetic variants in the folate pathway and the risk of neural tube defects: a meta-analysis of the published literature.
abstract: BACKGROUND
  Neural Tube Defects (NTDs) are among the most prevalent and most severe congenital malformations worldwide. Polymorphisms in key genes involving the folate pathway have been reported to be associated with the risk of NTDs. However, the results from these published studies are conflicting. We surveyed the literature (1996-2011) and performed a comprehensive meta-analysis to provide empirical evidence on the association.
  
  
  RESULTS
  We investigated the effects of 5 genetic variants from 47 study populations, for a total of 85 case-control comparisons MTHFR C677T (42 studies; 4374 cases, 7232 controls), MTHFR A1298C (22 studies; 2602 cases, 4070 controls), MTR A2756G (9 studies; 843 cases, 1006 controls), MTRR A66G (8 studies; 703 cases, 1572 controls), and RFC-1 A80G (4 studies; 1107 cases, 1585 controls). We found a convincing evidence of dominant effects of MTHFR C677T (OR 1.23; 95%CI 1.07-1.42) and suggestive evidence of RFC-1 A80G (OR 1.55; 95%CI 1.24-1.92). However, we found no significant effects of MTHFR A1298C, MTR A2756G, MTRR A66G in risk of NTDs in dominant, recessive or in allelic models.
  
  
  CONCLUSIONS
  Our meta-analysis strongly suggested a significant association of the variant MTHFR C677T and a suggestive association of RFC-1 A80G with increased risk of NTDs. However, other variants involved in folate pathway do not demonstrate any evidence for a significant marginal association on susceptibility to NTDs.
authors.affiliation: Department of Epidemiology and Biostatistics and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ti
authors.initials: T
authors.lastname: Zhang
authors.forename: Jiao
authors.initials: J
authors.lastname: Lou
authors.forename: Rong
authors.initials: R
authors.lastname: Zhong
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Li
authors.initials: L
authors.lastname: Zou
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.forename: Xuzai
authors.initials: X
authors.lastname: Lu
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
authors.forename: Guanglian
authors.initials: G
authors.lastname: Xiong
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D005287:Ferredoxin-NADP Reductase / Q000235:genetics; D005492:Folic Acid / Q000378:metabolism*; D005787:Gene Frequency; D006801:Humans; D053858:Metabolic Networks and Pathways; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D009436:Neural Tube Defects / Q000235:genetics* / Q000378:metabolism*; D016017:Odds Ratio; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D011110:Polymorphism, Genetic; D017594:Publication Bias; D051818:Replication Protein C / Q000235:genetics
chemical_list: C081632:RFC1 protein, human; D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D017853:Phosphotransferases (Alcohol Group Acceptor); C021787:5-methylthioribose kinase; D051818:Replication Protein C