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

Prenatal Diagnosis - Tập 28 Số 6 - Trang 485-493 - 2008
Raf Brouns1, N. T. C. Ursem2, Jan Lindemans1, Wim C.J. Hop3, Saskia M.F. Pluijm4, Eric A.P. Steegers2, Régine P.M. Steegers‐Theunissen5,3,2,6
1Department of Clinical Chemistry, Erasmus MC University Medical Center, Rotterdam, The Netherlands
2Department of Obstetrics and Gynaecology, Division of Obstetrics and Prenatal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
3Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
4Department of Public Health, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
5Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands
6Department of Paediatrics, Division of Paediatric Cardiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

Tóm tắt

AbstractObjectiveTo investigate the associations between biomarkers and genetic variants involved in homocysteine metabolism and the risk of complex birth defects.MethodsTotal 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.ResultsSignificantly lower cobalamin and higher apo‐TC, apo‐HC, tHcy and folate concentrations were determined in amniotic fluids of cases compared with controls (p⩽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.ConclusionThe MTHFR 677C > T polymorphism in conjunction with reduced folate‐ and/or cobalamin status may increase the risk of complex birth defects. Copyright © 2008 John Wiley & Sons, Ltd.

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Prenatal Diagnosis

Tập 28 Số 6

485-493

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