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

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.