title: Association between maternal single nucleotide polymorphisms in genes regulating glucose metabolism and risk for neural tube defects in offspring.
abstract: BACKGROUND
  Maternal pregestational hyperglycemia, diabetes, and obesity are well-established risk factors for neural tube defects (NTDs). As a common underlying mechanism, the imbalance of glucose homeostasis is directly related to the development of NTDs. Polymorphisms in genes regulating glucose metabolism in women may impact their chance of having an NTD-affected pregnancy.
  
  
  METHODS
  We conducted a two-stage case-control study to investigate the association between maternal genetic variants in genes regulating glucose metabolism and risk for NTDs. The cases were 547 women who gave birth to a child with an NTD (anencephaly, spina bifida, or encephalocele); the controls were 543 women who gave birth to a full-term healthy infant. In the first stage, 12 single nucleotide polymorphisms were genotyped in 160 cases and 162 controls. In the second stage, five single nucleotide polymorphisms found in the first stage and potentially associated with NTD risk were genotyped for validation, in an additional 387 cases and 381 controls.
  
  
  RESULTS
  Combined analysis of data from the two stages showed an association between maternal AA genotype of GCKR rs780094 and increased risk for total NTDs [odds ratio, 1.73; 95% confidence interval, 1.16-2.59) and spina bifida subtype [odds ratio, 1.83; 95% confidence interval, 1.16-2.88). No association was found between the other four single nucleotide polymorphisms (LEPR rs1137100, HK1 rs748235, HHEX rs5015480, KCNQ1 rs2237892) and NTD risk.
  
  
  CONCLUSIONS
  The AA genotype in maternal GCKR rs780094 is associated with an increased risk for NTDs and spina bifida in the Chinese population.
authors.affiliation: Institute of Reproductive and Child Health / Ministry of Health Key Laboratory of Reproductive Health, School of Public Health, Peking University, Beijing, China.
authors.forename: Yunting
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Institute of Reproductive and Child Health / Ministry of Health Key Laboratory of Reproductive Health, School of Public Health, Peking University, Beijing, China.
authors.forename: Lin-lin
authors.initials: LL
authors.lastname: Wang
authors.affiliation: Institute of Reproductive and Child Health / Ministry of Health Key Laboratory of Reproductive Health, School of Public Health, Peking University, Beijing, China.
authors.forename: Deqing
authors.initials: D
authors.lastname: Yi
authors.affiliation: Institute of Reproductive and Child Health / Ministry of Health Key Laboratory of Reproductive Health, School of Public Health, Peking University, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.affiliation: Institute of Reproductive and Child Health / Ministry of Health Key Laboratory of Reproductive Health, School of Public Health, Peking University, Beijing, China.
authors.forename: Jufen
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Reproductive and Child Health / Ministry of Health Key Laboratory of Reproductive Health, School of Public Health, Peking University, Beijing, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Reproductive and Child Health / Ministry of Health Key Laboratory of Reproductive Health, School of Public Health, Peking University, Beijing, China.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Ren
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006593:Hexokinase / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D009436:Neural Tube Defects / Q000453:epidemiology* / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D054411:Receptors, Leptin / Q000235:genetics; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C485100:GCKR protein, human; C078492:HHEX protein, human; D018398:Homeodomain Proteins; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; C515448:LEPR protein, human; D054411:Receptors, Leptin; D014157:Transcription Factors; C472074:HK1 protein, human; D006593:Hexokinase; D005947:Glucose
keywords: glucose metabolism; neural tube defects; single nucleotide polymorphism