title: Investigations of single nucleotide polymorphisms in folate pathway genes in Chinese families with neural tube defects.
abstract: OBJECTIVE
  We investigated the hypothesis that there are interactions between SNPs in folate metabolism pathway genes and environmental risk factors to the etiology of neural tube defects (NTDs).
  
  
  METHODS
  In 602 Chinese families, 609 aborted fetus tissues or blood samples were collected from NTD individuals, and 1106 parental blood samples were detected as controls. We analyzed 28 SNPs in 12 folate pathway genes. Folate supplementation, gestational diabetes mellitus (GDM) and medicine administration before and during pregnancy were investigated. Case-parental control study and transmission/disequilibrium tests were performed according to environmental cofactor stratification.
  
  
  RESULTS
  Association between 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C>T and NTDs was significant in all stratifications (all P<.05), and synergistic effects of no folate supplementation and GDM were shown on NTD occurrence. 5-Methyltetrahydrofolate-homocysteine methyltransferase (MTHM) 501A>G in case of GDM, and betaine-homocysteine methyltransferase (BHMT) 716G>A in case of no folate supplementation significantly associated with NTDs (both P<.05), whereas the two genotypes alone did not significantly associate with NTDs (both P>.05).
  
  
  CONCLUSIONS
  MTHFR 677C>T genotype, especially in case of no folate supplementation and GDM, promotes NTD occurrence. MTHM 501A>G only in case of GDM, and BHMT 716G>A only in case of no folate supplementation contribute to the etiology of NTDs.
authors: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Pediatrics, Xiangyang Central Hospital, Xiangyang, China. Electronic address: drliujian@gmail.com.
authors: Jian
authors: J
authors: Liu
authors: Department of Neurology, Xiangyang Central Hospital, Xiangyang, China. Electronic address: qijingys@126.com.
authors: Jing
authors: J
authors: Qi
authors: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: yuxiao4249@sina.com.
authors: Xiao
authors: X
authors: Yu
authors: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: zjoyjay@163.com.
authors: Jie
authors: J
authors: Zhu
authors: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: zhlx1981508@yahoo.com.cn.
authors: Lixia
authors: L
authors: Zhang
authors: Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: qning@tjh.tjmu.edu.cn.
authors: Qin
authors: Q
authors: Ning
authors: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: xpluo@tjh.tjmu.edu.cn.
authors: Xiaoping
authors: X
authors: Luo
mesh_terms: D050940:Betaine-Homocysteine S-Methyltransferase / Q000235:genetics; D002681:China; D005192:Family Health; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics; D005492:Folic Acid / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D009436:Neural Tube Defects / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C494548:BHMT protein, human; D050940:Betaine-Homocysteine S-Methyltransferase
keywords: Case-parental control study; Folate; Genetic association; Neural tube defects; Single nucleotide polymorphisms; Spina bifida