title: Uncoupling protein 2 polymorphisms as risk factors for NTDs.
abstract: BACKGROUND
  Both environmental and genetic factors are involved in the etiology of NTDs. Inadequate folate intake and obesity are important environmental risk factors. Several folate-related genetic variants have been identified as risk factors; however, little is known about how genetic variants relate to the increased risk seen in obese women. Uncoupling Protein 2 (UCP2) is an attractive candidate to screen for NTD risk because of its possible role in obesity as well as energy metabolism, type-2 diabetes, and the regulation of reactive oxygen species. Interestingly, a previous study found that a common UCP2 compound homozygous genotype was associated with a threefold increase in NTD risk.
  
  
  METHODS
  We evaluated three polymorphisms, -866G>A, A55V, and the 3'UTR 45 bp insertion/deletion, as risk factors for NTDs in Irish NTD cases (n = 169), their mothers (n = 163), their fathers (n = 167), and normal control subjects (n = 332).
  
  
  RESULTS
  Allele and genotype frequencies were not significantly different when comparing NTD mothers, NTD fathers, or affected children to controls. Additionally, the previously reported risk genotype (combined homozygosity of 55VV and 3'UTR 45 bp deletion/deletion) was not present at a higher frequency in any NTD group when compared to controls.
  
  
  CONCLUSIONS
  In our Irish study population, UCP2 polymorphisms did not influence NTD risk. Moreover, the prevalence of this allele in other populations was similar to the Irish prevalence but far lower than reported in the previous NTD study, suggesting that this previous finding of an association with NTDs might have been due to an unrepresentative study sample.
authors.affiliation: Molecular Pathogenesis Section, Genome Technology Branch, National Human Genome Research Institute, 50 South Drive, Bethesda, MD 20892-8004, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Mitchell
authors.forename: Faith
authors.initials: F
authors.lastname: Pangilinan
authors.forename: Julie
authors.initials: J
authors.lastname: Van der Meer
authors.forename: Anne M
authors.initials: AM
authors.lastname: Molloy
authors.forename: James
authors.initials: J
authors.lastname: Troendle
authors.forename: Mary
authors.initials: M
authors.lastname: Conley
authors.forename: Peadar N
authors.initials: PN
authors.lastname: Kirke
authors.forename: John M
authors.initials: JM
authors.lastname: Scott
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Brody
authors.forename: James L
authors.initials: JL
authors.lastname: Mills
mesh_terms: D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D007494:Ireland; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics*; D009436:Neural Tube Defects / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D000071246:Uncoupling Protein 2
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2