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Polymorphisms in genes related to folate and cobalamin metabolism and the associations with complex birth defects.

Abstract

OBJECTIVE

To investigate the associations between biomarkers and genetic variants involved in homocysteine metabolism and the risk of complex birth defects.

METHODS

Total homocysteine (tHcy), folate, cobalamin, apo-transcobalamin (apo-TC) and apo-haptocorrin (apo-HC) were measured in the amniotic fluid of 82 women who were pregnant with a child having a complex birth defect, such as neural tube defect, cleft lip and/or palate, heart defect or omphalocele, and in 110 women pregnant with a non-malformed child. The determined genotypes of the child comprised of 5, 10-methylenetetrahydrofolate reductase (MTHFR 677C > T, 1298A > C), methionine synthase (MTR 2756A > G), methionine synthase reductase (MTRR 66A > G) and transcobalamin (TCN2 776C > G). Univariate and multivariate logistic regression analyses were performed.

RESULTS

Significantly lower cobalamin and higher apo-TC, apo-HC, tHcy and folate concentrations were determined in amniotic fluids of cases compared with controls (p< or =0.001). Logistic regression analysis revealed that after adjustment for maternal age, children carrying the MTHFR 677T allele showed a four-fold increased risk of having a complex birth defect, OR (95% CI) = 4.0 (1.1-15.4). Other genotypes did not show significant associations.

CONCLUSION

The MTHFR 677C > T polymorphism in conjunction with reduced folate- and/or cobalamin status may increase the risk of complex birth defects.

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  • Authors+Show Affiliations

    ,

    Department of Clinical Chemistry, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

    , , , , ,

    Source

    Prenatal diagnosis 28:6 2008 Jun pg 485-93

    MeSH

    5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
    Adult
    Amniotic Fluid
    Case-Control Studies
    Child
    Congenital Abnormalities
    Female
    Ferredoxin-NADP Reductase
    Folic Acid
    Genetic Predisposition to Disease
    Genotype
    Homocysteine
    Humans
    Methylenetetrahydrofolate Reductase (NADPH2)
    Polymorphism, Genetic
    Pregnancy
    Risk Factors
    Transcobalamins
    Vitamin B 12

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    18435414

    Citation

    Brouns, R, et al. "Polymorphisms in Genes Related to Folate and Cobalamin Metabolism and the Associations With Complex Birth Defects." Prenatal Diagnosis, vol. 28, no. 6, 2008, pp. 485-93.
    Brouns R, Ursem N, Lindemans J, et al. Polymorphisms in genes related to folate and cobalamin metabolism and the associations with complex birth defects. Prenat Diagn. 2008;28(6):485-93.
    Brouns, R., Ursem, N., Lindemans, J., Hop, W., Pluijm, S., Steegers, E., & Steegers-Theunissen, R. (2008). Polymorphisms in genes related to folate and cobalamin metabolism and the associations with complex birth defects. Prenatal Diagnosis, 28(6), pp. 485-93. doi:10.1002/pd.2006.
    Brouns R, et al. Polymorphisms in Genes Related to Folate and Cobalamin Metabolism and the Associations With Complex Birth Defects. Prenat Diagn. 2008;28(6):485-93. PubMed PMID: 18435414.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Polymorphisms in genes related to folate and cobalamin metabolism and the associations with complex birth defects. AU - Brouns,R, AU - Ursem,N, AU - Lindemans,J, AU - Hop,W, AU - Pluijm,S, AU - Steegers,E, AU - Steegers-Theunissen,R, PY - 2008/4/26/pubmed PY - 2008/10/24/medline PY - 2008/4/26/entrez SP - 485 EP - 93 JF - Prenatal diagnosis JO - Prenat. Diagn. VL - 28 IS - 6 N2 - OBJECTIVE: To investigate the associations between biomarkers and genetic variants involved in homocysteine metabolism and the risk of complex birth defects. METHODS: Total homocysteine (tHcy), folate, cobalamin, apo-transcobalamin (apo-TC) and apo-haptocorrin (apo-HC) were measured in the amniotic fluid of 82 women who were pregnant with a child having a complex birth defect, such as neural tube defect, cleft lip and/or palate, heart defect or omphalocele, and in 110 women pregnant with a non-malformed child. The determined genotypes of the child comprised of 5, 10-methylenetetrahydrofolate reductase (MTHFR 677C > T, 1298A > C), methionine synthase (MTR 2756A > G), methionine synthase reductase (MTRR 66A > G) and transcobalamin (TCN2 776C > G). Univariate and multivariate logistic regression analyses were performed. RESULTS: Significantly lower cobalamin and higher apo-TC, apo-HC, tHcy and folate concentrations were determined in amniotic fluids of cases compared with controls (p< or =0.001). Logistic regression analysis revealed that after adjustment for maternal age, children carrying the MTHFR 677T allele showed a four-fold increased risk of having a complex birth defect, OR (95% CI) = 4.0 (1.1-15.4). Other genotypes did not show significant associations. CONCLUSION: The MTHFR 677C > T polymorphism in conjunction with reduced folate- and/or cobalamin status may increase the risk of complex birth defects. SN - 0197-3851 UR - https://www.unboundmedicine.com/medline/citation/18435414/Polymorphisms_in_genes_related_to_folate_and_cobalamin_metabolism_and_the_associations_with_complex_birth_defects_ L2 - https://doi.org/10.1002/pd.2006 DB - PRIME DP - Unbound Medicine ER -