Low fasting methionine concentration as a novel risk factor for recurrent venous thrombosis

Miranda B. A. J. Keijzer; Martin den Heijer; George F. Borm; Henk J. Blom; Stein Emil Vollset; Ad R. M. M. Hermus; Per M. Ueland

doi:10.1160/TH06-04-0187

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 96(04): 492-497
DOI: 10.1160/TH06-04-0187

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Low fasting methionine concentration as a novel risk factor for recurrent venous thrombosis

Miranda B. A. J. Keijzer

¹Department of Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

,

Martin den Heijer

¹Department of Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

²Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

,

George F. Borm

²Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

,

Henk J. Blom

³Laboratory of Paediatrics and Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

,

Stein Emil Vollset

⁴Locus for Homocysteine and Related Vitamins, University of Bergen, Bergen, Norway

,

Ad R. M. M. Hermus

¹Department of Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

,

Per M. Ueland

⁴Locus for Homocysteine and Related Vitamins, University of Bergen, Bergen, Norway

› Author Affiliations

Abstract

Summary

Hyperhomocysteinemia is a risk factor for venous thrombosis, but the underlying mechanism is unclear. If the thiol-group of homocysteine interferes with components of the clotting system, we expect that high cysteine will be alsoa risk factor for venous thrombosis. If high homocysteine reflects a disturbed methyl-group donation by S-adenosylmethionine, we expect that low methionine will be a risk factor for thrombosis. We performeda case-control study in 185 patients with recurrent venous thrombosis and in 500 control subjects.

We determined methionine, homocysteine, cysteine and assessed the associated thrombotic risk. Low fasting methionine was associated with an increased risk on recurrent venous thrombosis [OR_{bottom vs. top quartile} = 3.3 (95%CI 1.9–5.7)]. Low methionine remained a risk factor [OR_{bottom vs. top quartile}= 3.5 (95%CI 2.0–6.0)] after adjusting for homocysteine and cysteine, whereas the thrombotic risk for homocysteine was lost [OR= 1.0 (95%CI 0.6–1.9)] after adjustment. Cysteine yielded a highest odds ratio of 2.1_{top vs. bottom quartile} (95%CI 1.0–4.0) after adjustment. In conclusion, we found that low fasting methionine is a risk factor for recurrent venous thrombosis.This risk association was stronger for methionine than for homocysteine or cysteine.This supports the hypothesis that impaired methylation may be involved in the pathogenesis of venous thrombosis.

Keywords

Methionine - homocysteine - cysteine - venous thrombosis

Full Text

References

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