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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

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1437-4331
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Volume 44, Issue 11 (Nov 2006)

Issues

MTRR 66A>G polymorphism in relation to congenital heart defects

Ingrid M. van Beynum
  • Children's Heart Centre, Radboud University Nijmegen Medical Centre, The Netherlands
/ Margreet Kouwenberg
  • Department of Paediatrics, Radboud University Nijmegen Medical Centre, The Netherlands
/ Livia Kapusta
  • Children's Heart Centre, Radboud University Nijmegen Medical Centre, The Netherlands
/ Martin den Heijer
  • Department of Endocrinology, Radboud University Nijmegen Medical Centre, The Netherlands and Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Centre, The Netherlands
/ Ivon J.M. van der Linden
  • Laboratory of Paediatrics and Neurology, Radboud University Nijmegen Medical Centre, The Netherlands
/ Otto Daniels
  • Children's Heart Centre, Radboud University Nijmegen Medical Centre, The Netherlands
/ Henk J. Blom
  • Laboratory of Paediatrics and Neurology, Radboud University Nijmegen Medical Centre, The Netherlands

Abstract

Background: Evidence is accumulating that periconceptional folic acid supplementation may prevent congenital heart defects (CHD). The methionine synthase reductase (MTRR) enzyme restores methionine synthase (MTR) enzyme activity and therefore plays an essential role in the folate- and vitamin B12-dependent remethylation of homocysteine to methionine. We studied the influence of the MTRR 66A>G polymorphism on CHD risk. In addition, possible interaction between this variant and plasma methylmalonic acid (MMA) concentrations, as an indicator of intracellular vitamin B12 status, was investigated.

Methods: Case-control and case-parental studies were conducted to explore this association. In total, 169 CHD patients and 213 child controls, and 159 mothers with a CHD-affected child and 245 female controls were included.

Results: The maternal MTRR 66AG and GG vs. AA genotypes revealed an odds ratio (OR) of 1.3 (95% CI 0.72–2.20) and 1.3 (0.71–2.37), respectively. Family-based transmission disequilibrium analysis did not reveal a significant association of the foetal 66G allele with the development of a heart defect in children (χ2=2.94, p=0.086). Maternal 66GG genotype in combination with high MMA concentration (above the 80th percentile) was associated with a three-fold (OR 3.3, 95% CI 0.86–12.50) increased risk for all types of CHD in offspring.

Conclusions: These data indicate that maternal MTRR 66A>G polymorphism is not a risk factor for CHD. Maternal MTRR 66GG genotype with compromised vitamin B12 status may possibly result in increased CHD risk. In addition to folate, vitamin B12 supplementation may contribute to the prevention of CHD.

Clin Chem Lab Med 2006;44:1317–23.

Keywords: congenital heart defects; methionine synthase reductase; methylmalonic acid

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About the article

Corresponding author: I.M. van Beynum, Children's Heart Centre, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands Phone: +31-24-3614427, Fax: +31-24-3619052,


Received: July 19, 2006

Accepted: September 10, 2006

Published in Print: 2006-11-01


Citation Information: Clinical Chemical Laboratory Medicine, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2006.254. Export Citation

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