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Single nucleotide polymorphisms in the transcobalamin gene: relationship with transcobalamin concentrations and risk for neural tube defects.
Eur J Hum Genet 2002; 10(7):433-8EJ

Abstract

Homocysteine levels are elevated in mothers of neural tube defect (NTD) children, which may be due to a disturbed folate or vitamin B12 metabolism. Vitamin B12 is transported to the tissues by transcobalamin (TC). We previously showed that a low holo-TC/total-TC ratio is a risk factor for NTD, possibly due to an impaired binding of vitamin B12 to TC. The coding region of the TC gene of 12 individuals was analysed for genetic variations responsible for a disturbed vitamin B12 binding. The influence of the genetic variations observed on total-TC, holo-TC, holo-TC/total-TC, erythrocyte vitamin B12, plasma homocysteine concentrations and risk for NTD was explored in 42 mothers of a child with NTD and in 73 female controls. Direct sequencing analyses revealed five single nucleotide polymorphisms (SNPs). Three SNPs affected total-TC concentrations, whereas two SNPs seem to affect the binding of vitamin B12. None of the genotypes defined by the SNPs had a significant effect on homocysteine levels, or was associated with an increased NTD risk. Among the five SNPs observed only P259R could partly explain the reduced proportion of vitamin B12 bound to TC, which has been associated with an increased risk for having a child with NTD. Some of the variants studied affected total-TC and holo-TC/total-TC ratio but a larger study population is required to elucidate whether these SNPs influence delivery of vitamin B12 to the tissue, influence homocysteine levels and whether they are associated with an increased NTD risk.

Authors+Show Affiliations

University Medical Center Nijmegen, Department of Pediatrics, Laboratory of Pediatrics and Neurology, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12107818

Citation

Afman, Lydia A., et al. "Single Nucleotide Polymorphisms in the Transcobalamin Gene: Relationship With Transcobalamin Concentrations and Risk for Neural Tube Defects." European Journal of Human Genetics : EJHG, vol. 10, no. 7, 2002, pp. 433-8.
Afman LA, Lievers KJ, van der Put NM, et al. Single nucleotide polymorphisms in the transcobalamin gene: relationship with transcobalamin concentrations and risk for neural tube defects. Eur J Hum Genet. 2002;10(7):433-8.
Afman, L. A., Lievers, K. J., van der Put, N. M., Trijbels, F. J., & Blom, H. J. (2002). Single nucleotide polymorphisms in the transcobalamin gene: relationship with transcobalamin concentrations and risk for neural tube defects. European Journal of Human Genetics : EJHG, 10(7), pp. 433-8.
Afman LA, et al. Single Nucleotide Polymorphisms in the Transcobalamin Gene: Relationship With Transcobalamin Concentrations and Risk for Neural Tube Defects. Eur J Hum Genet. 2002;10(7):433-8. PubMed PMID: 12107818.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Single nucleotide polymorphisms in the transcobalamin gene: relationship with transcobalamin concentrations and risk for neural tube defects. AU - Afman,Lydia A, AU - Lievers,Karin J A, AU - van der Put,Nathalie M J, AU - Trijbels,Frans J M, AU - Blom,Henk J, PY - 2002/02/11/received PY - 2002/04/16/revised PY - 2002/04/26/accepted PY - 2002/7/11/pubmed PY - 2003/5/20/medline PY - 2002/7/11/entrez SP - 433 EP - 8 JF - European journal of human genetics : EJHG JO - Eur. J. Hum. Genet. VL - 10 IS - 7 N2 - Homocysteine levels are elevated in mothers of neural tube defect (NTD) children, which may be due to a disturbed folate or vitamin B12 metabolism. Vitamin B12 is transported to the tissues by transcobalamin (TC). We previously showed that a low holo-TC/total-TC ratio is a risk factor for NTD, possibly due to an impaired binding of vitamin B12 to TC. The coding region of the TC gene of 12 individuals was analysed for genetic variations responsible for a disturbed vitamin B12 binding. The influence of the genetic variations observed on total-TC, holo-TC, holo-TC/total-TC, erythrocyte vitamin B12, plasma homocysteine concentrations and risk for NTD was explored in 42 mothers of a child with NTD and in 73 female controls. Direct sequencing analyses revealed five single nucleotide polymorphisms (SNPs). Three SNPs affected total-TC concentrations, whereas two SNPs seem to affect the binding of vitamin B12. None of the genotypes defined by the SNPs had a significant effect on homocysteine levels, or was associated with an increased NTD risk. Among the five SNPs observed only P259R could partly explain the reduced proportion of vitamin B12 bound to TC, which has been associated with an increased risk for having a child with NTD. Some of the variants studied affected total-TC and holo-TC/total-TC ratio but a larger study population is required to elucidate whether these SNPs influence delivery of vitamin B12 to the tissue, influence homocysteine levels and whether they are associated with an increased NTD risk. SN - 1018-4813 UR - https://www.unboundmedicine.com/medline/citation/12107818/Single_nucleotide_polymorphisms_in_the_transcobalamin_gene:_relationship_with_transcobalamin_concentrations_and_risk_for_neural_tube_defects_ L2 - http://dx.doi.org/10.1038/sj.ejhg.5200830 DB - PRIME DP - Unbound Medicine ER -