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The maternal homocysteine pathway is influenced by riboflavin intake and MTHFR polymorphisms without affecting the risk of orofacial clefts in the offspring

European Journal of Clinical Nutrition volume 64, pages 266–273 (2010)Cite this article

Abstract

Background/Objectives:

Riboflavin is a cofactor for the 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme involved in the homocysteine pathway. The aim of this study was to investigate the effects of maternal riboflavin intake and two MTHFR polymorphisms (677C>T; Ala222Val and 1298A>C; Glu429Ala substitutions) on the biomarkers of the homocysteine pathway, and investigate the risk of having offspring with an orofacial cleft (OFC).

Subjects/Methods:

In a case–control study design, dietary riboflavin intake and the MTHFR 677C>T and 1298A>C polymorphisms were evaluated in 123 OFC and 108 control mothers by using food frequency questionnaires and blood samples. Homocysteine (tHcy), folate and vitamin B12 concentrations in blood were analyzed in 70 cases and 68 controls. Linear and logistic regression analyses were applied.

Results:

At 14 months postpartum riboflavin intake and MTHFR 677C>T and 1298A>C genotypes were not significantly different between cases and controls. The 677TT genotype showed lower folate concentrations compared to C-allele carriers with a mean difference of 2.8 nmol/l in serum and 174 nmol/l in red blood cell (both P's=0.01). Every mg per day increase of dietary riboflavin intake was positively associated with increase in vitamin B12 concentration by 52.1% (P<0.01). This effect was most pronounced in MTHFR 677TT homozygotes (205.1%, P=0.03). The riboflavin-adjusted MTHFR 677TT and 1298CC genotypes showed a trend toward an increasing risk for OFC, adjusted odds ratio 1.7 (confidence interval (95% CI), 0.7–4.5) and 1.6 (95% CI, 0.7–4.2), respectively.

Conclusions:

Maternal riboflavin intake is significantly associated with biomarkers of the homocysteine pathway, with the strongest effects in MTHFR 677TT homozygotes. The maternal risk of having OFC offspring, however, is not associated with dietary riboflavin intake.

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Acknowledgements

This study was supported by a grant of the Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, the Netherlands (1997) and the Mother and Child Centre, Department of Obstetrics and Gynaecology, Division of Obstetrics and Prenatal Medicine, Erasmus University Medical Centre, Rotterdam, the Netherlands.

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Erasmus University Medical Centre, Rotterdam, The Netherlands

    M Vujkovic, E A Steegers & R P Steegers-Theunissen

  2. Department of Internal Medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands

    J van Meurs, N Yazdanpanah & A G Uitterlinden

  3. Department of Epidemiology, Biostatistics and Health Technology Assessment, Radboud University Medical Centre, Nijmegen, The Netherlands

    I A van Rooij

  4. Department of Epidemiology and Biostatistics, Erasmus University Medical Centre, Rotterdam, The Netherlands

    A G Uitterlinden & R P Steegers-Theunissen

  5. Division Paediatric Cardiology, Department of Paediatrics, Erasmus University Medical Centre, Rotterdam, The Netherlands

    R P Steegers-Theunissen

  6. Department of Clinical Genetics, Erasmus University Medical Centre, Rotterdam, The Netherlands

    R P Steegers-Theunissen

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  1. M Vujkovic
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  2. E A Steegers
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Correspondence to R P Steegers-Theunissen.

Additional information

Contributors: MV performed statistical analysis of the data and drafted the first version of the paper. JvM and AGU were involved in the interpretation of the data and all revisions of the paper. NY contributed to the statistical analysis and all revisions of the paper. IAvR carried out the data collection and contributed to the final version of the paper. EAS supervised the study and contributed to all revisions of the paper. RPS-T initiated the study, hypothesis, design, supervised the study, contributing to all versions of the paper.

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Vujkovic, M., Steegers, E., van Meurs, J. et al. The maternal homocysteine pathway is influenced by riboflavin intake and MTHFR polymorphisms without affecting the risk of orofacial clefts in the offspring. Eur J Clin Nutr 64, 266–273 (2010). https://doi.org/10.1038/ejcn.2009.138

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