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Clinical Chemistry and Laboratory Medicine (CCLM)

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

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Volume 45, Issue 4 (Apr 2007)


Associations of common polymorphisms in the thymidylate synthase, reduced folate carrier and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine monophosphate cyclohydrolase genes with folate and homocysteine levels and venous thrombosis risk

Henkjan Gellekink
  • 1Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands and Department of Endocrinology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
/ Henk J. Blom
  • 2Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
/ Martin den Heijer
  • 3Department of Endocrinology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands and Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Published Online: 2007-04-17 | DOI: https://doi.org/10.1515/CCLM.2007.091


Background: Folate is important in purine and thymidylate synthesis and, via homocysteine remethylation, facilitates S-adenosylmethionine-dependent transmethylation. Low folate availability leads to hyperhomocysteinemia, which is a risk factor for arterial vascular disease and venous thrombosis. Genetic variation in folate-metabolizing genes may affect folate availability and hence confer a greater risk of venous thrombosis.

Methods: We genotyped the thymidylate synthase (TYMS) 28-bp repeat and 6-bp deletion, and the reduced folate carrier (RFC1) 80G>A and AICAR transformylase/inosine monophosphate (IMP) cyclohydrolase (ATIC) 346C>G polymorphisms in population-based controls (n=431), and assessed their effect on plasma total homocysteine (tHcy), and serum and red blood cell (RBC) folate. We investigated the associations between these variants and disease risk in a retrospective case-control study on recurrent venous thrombosis (n=173) as well.

Results: None of the genotypes, alone or in combination, were associated with major changes in tHcy. However, the TYMS 28-bp repeat was associated with serum and RBC folate levels. We found no evidence that the genetic variants studied were associated with recurrent venous thrombosis risk.

Conclusions: The TYMS 28-bp repeat and 6-bp deletion, and RFC1 80G>A and ATIC 346C>G polymorphisms are not associated with tHcy, but we did observe an association between the TYMS 28-bp repeat and serum and RBC folate in a general population. None of the polymorphisms was associated with recurrent venous thrombosis risk.

Clin Chem Lab Med 2007;45:471–6.

Keywords: folate; homocysteine; polymorphisms; recurrent venous thrombosis

About the article

Corresponding author: Martin den Heijer, MD, PhD, Department of Endocrinology (471), Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands Phone: +31-24-3614599, Fax: +31-24-3618809,

Received: 2006-10-17

Accepted: 2006-12-22

Published Online: 2007-04-17

Published in Print: 2007-04-01

Citation Information: Clinical Chemical Laboratory Medicine, ISSN (Online) 14346621, ISSN (Print) 14374331, DOI: https://doi.org/10.1515/CCLM.2007.091. Export Citation

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