Evaluation of transcobalamin II polymorphisms as neural tube defect risk factors in an Irish population

• Published in: Birth defects research. A Clinical and molecular teratology Vol. 73; no. 4; pp. 239 - 244
• Main Authors: Swanson, Deborah A., Pangilinan, Faith, Mills, James L., Kirke, Peadar N., Conley, Mary, Weiler, Andrea, Frey, Tiffany, Parle-McDermott, Anne, O'Leary, Valerie B., Seltzer, Rebecca R., Moynihan, Kathryn A., Molloy, Anne M., Burke, Helen, Scott, John M., Brody, Lawrence C.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-04-2005; Wiley
• Subjects: Alleles; Biological and medical sciences; Case-Control Studies; Diseases of the osteoarticular system; Embryology: invertebrates and vertebrates. Teratology; Female; folate; Fundamental and applied biological sciences. Psychology; Gene Frequency; Humans; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical sciences; neural tube defects; Neural Tube Defects - ethnology; Neural Tube Defects - genetics; Polymorphism, Single Nucleotide; Risk Factors; spina bifida; Teratology. Teratogens; transcobalamin II gene; Transcobalamins - genetics; Vitamin B 12 - metabolism; vitamin B12; Europe; Ireland; Human; Evaluation; Nervous system diseases; Genetic variability; Diseases of the osteoarticular system; Genotype; Spine disease; Congenital disease; Epidemiology; Transcobalamin II; Neural tube defect; Irish; Spina bifida; Malformation; Risk factor; Public health; Polymorphism
• ISSN: 1542-0752; 1542-0760
• DOI: 10.1002/bdra.20122

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 B12 (as methylcobalamin) is a cofactor for methionine synthase, an enzyme that plays a key role in folate metabolism. Alterations in vitamin B12 metabolism may influence the development of NTDs. Low levels of maternal plasma vitamin B12 and reduced binding of vitamin B12 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 B12 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 Birth Defects Research (Part A), 2005. Published 2005 Wiley‐Liss, Inc.