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Prenat Diagn. 2008 Jun;28(6):485-93. doi: 10.1002/pd.2006.

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

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



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


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.


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.


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

[Indexed for MEDLINE]

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