title: Evaluation of transcobalamin II polymorphisms as neural tube defect risk factors in an Irish population.
abstract: BACKGROUND
  Decreased maternal folate levels are associated with having a child with a neural tube defect (NTD), and periconceptual folic acid supplementation reduces this risk by >50%. Vitamin B(12) (as methylcobalamin) is a cofactor for methionine synthase, an enzyme that plays a key role in folate metabolism. Alterations in vitamin B(12) metabolism may influence the development of NTDs. Low levels of maternal plasma vitamin B(12) and reduced binding of vitamin B(12) by transcobalamin II (TCII) are independent risk factors for NTDs. TCII levels are altered in the amniotic fluid of pregnancies affected by NTDs. Given this evidence, inherited variants in genes involved in vitamin B(12) trafficking such as TCII are candidate NTD risk factors.
  
  
  METHODS
  We used case/control and family-based association methods to investigate whether six common polymorphisms in the TCII gene influence NTD risk. TCII genotypes were determined for more than 300 Irish NTD families and a comparable number of Irish controls.
  
  
  RESULTS
  Allele and genotype frequencies for each polymorphism did not differ between family members and controls.
  
  
  CONCLUSIONS
  These six TCII polymorphisms do not strongly influence NTD risk in the Irish population. The Supplementary Material for this article can be found on the Birth Defects Research (Part A) website: http://www.mrw.interscience.wiley.com/suppmat/1542-0752/suppmat/2005/73/v73.4.swanson.html
authors.affiliation: Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Swanson
authors.forename: Faith
authors.initials: F
authors.lastname: Pangilinan
authors.forename: James L
authors.initials: JL
authors.lastname: Mills
authors.forename: Peadar N
authors.initials: PN
authors.lastname: Kirke
authors.forename: Mary
authors.initials: M
authors.lastname: Conley
authors.forename: Andrea
authors.initials: A
authors.lastname: Weiler
authors.forename: Tiffany
authors.initials: T
authors.lastname: Frey
authors.forename: Anne
authors.initials: A
authors.lastname: Parle-McDermott
authors.forename: Valerie B
authors.initials: VB
authors.lastname: O'Leary
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Seltzer
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Moynihan
authors.forename: Anne M
authors.initials: AM
authors.lastname: Molloy
authors.forename: Helen
authors.initials: H
authors.lastname: Burke
authors.forename: John M
authors.initials: JM
authors.lastname: Scott
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Brody
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D009436:Neural Tube Defects / Q000208:ethnology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014155:Transcobalamins / Q000235:genetics*; D014805:Vitamin B 12 / Q000378:metabolism
chemical_list: D014155:Transcobalamins; D014805:Vitamin B 12