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 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
Swanson
Deborah A
DA
Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
Pangilinan
Faith
F
Mills
James L
JL
Kirke
Peadar N
PN
Conley
Mary
M
Weiler
Andrea
A
Frey
Tiffany
T
Parle-McDermott
Anne
A
O'Leary
Valerie B
VB
Seltzer
Rebecca R
RR
Moynihan
Kathryn A
KA
Molloy
Anne M
AM
Burke
Helen
H
Scott
John M
JM
Brody
Lawrence C
LC
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
D014155:Transcobalamins; D014805:Vitamin B 12