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Thromb Haemost 1998; 79(02): 254-258
DOI: 10.1055/s-0037-1614974
Letters to the Editor
Schattauer GmbH

Thermolabile Methylenetetrahydrofolate Reductase and Factor V Leiden in the Risk of Deep-Vein Thrombosis

Leo A. J. Kluijtmans
1   From the Department of Pediatrics, University Hospital Nijmegen, The Netherlands
,
Martin den Heijer
2   From the Department of International Medicine, Twee Steden Hospital, Tilburg, The Netherlands
,
Pieter H. Reitsma
3   From the Department of Hemostasis and Thrombosis, University Hospital Leiden, The Netherlands
,
Sandra G. Heil
1   From the Department of Pediatrics, University Hospital Nijmegen, The Netherlands
,
Henk J. Blom
1   From the Department of Pediatrics, University Hospital Nijmegen, The Netherlands
,
Frits R. Rosendaal
3   From the Department of Hemostasis and Thrombosis, University Hospital Leiden, The Netherlands
4   From the Department of Clinical Epidemiology, University Hospital Leiden, The Netherlands
› InstitutsangabenThis study was in part supported by grant 93.176 from The Netherlands Heart Foundation.
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Publikationsverlauf

Received 23. Juni 1997

Accepted after resubmission 24. September 1997

Publikationsdatum:
08. Dezember 2017 (online)

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Summary

Mild hyperhomocysteinemia is an established risk factor for both arteriosclerosis and thrombosis, and may be caused by genetic and environmental factors. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the cofactor for the methylation of homocysteine to methionine. Individuals with the thermolabile variant of MTHFR have decreased MTHFR activities, resulting in elevated plasma homocysteine concentrations. A homozygous 677C→T transition in the MTHFR gene has recently been identified as the cause of reduced enzyme activity and thermolability of the protein. We studied the frequency of the homozygous mutant (+/+) genotype in 471 patients with deep-vein thrombosis and 474 healthy controls enrolled in The Leiden Thrombophilia Study (LETS), its interaction with factor V Leiden, and assessed the association between the MTHFR genotypes and plasma homocysteine concentration. Homozygosity for the 677C→T polymorphism was observed in 47 (10%) patients, and in 47 (9.9%) controls (OR 1.01 [95% CI: 0.7-1.5]). No modified risk of the (+/+) genotype was observed in carriers of factor V Leiden. Our data suggest that, although the homozygous mutant genotype is associated with elevated plasma homocysteine concentrations, this homozygous mutation itself is not a genetic risk factor for deep-vein thrombosis, irrespective of factor V Leiden genotype.

 

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