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Thromb Haemost 2002; 88(05): 723-728
DOI: 10.1055/s-0037-1613292
Review Article
Schattauer GmbH

Interaction Between Hyperhomocysteinemia, Mutated Methylenetetrahydrofolatereductase (MTHFR) and Inherited Thrombophilic Factors in Recurrent Venous Thrombosis

Miranda B. A. J. Keijzer
1   Department of Endocrinology and Epidemiology and Biostatistics, University Medical Center Nijmegen
,
Martin den Heijer
1   Department of Endocrinology and Epidemiology and Biostatistics, University Medical Center Nijmegen
,
Henk J. Blom
2   Laboratory of Paediatrics and Neurology, University Medical Center Nijmegen
,
Gerard M. J. Bos
3   Department of Hematology, University Hospital Maastricht
,
Huub P. J. Willems
4   Department of Hematology, Leyenburg Hospital, The Hague
,
Wim B. J. Gerrits
4   Department of Hematology, Leyenburg Hospital, The Hague
,
Frits R. Rosendaal
5   Department of Clinical Epidemiology and Department of Hematology, Leiden University Medical Center; The Netherlands
› Author Affiliations
Further Information

Publication History

Received 05 November 2001

Accepted after resubmission 13 July 2002

Publication Date:
08 December 2017 (online)

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Summary

Venous thrombosis is a multicausal disease involving acquired and genetic factors. In this study we investigated a possible interaction between hyperhomocysteinemia (fasting or postload) and factor V Leiden or prothrombin G20210A on the risk of recurrent venous thrombosis. We also looked at the risk due to mutations in the MTHFR-gene (C677T and A1298C).

We performed a case-control study in 171 patients with a history of recurrent venous thrombosis and 461 control subjects from the general population. Hyperhomocysteinemia (fasting or 6 h after an oral methionine load) was defined as a homocysteine concentration above the 90th percentile of the distributions in the control group.

The odds ratio (adjusted for age and sex) for recurrent venous thrombosis was 1.8 (95%CI: 1.1 to 3.0) for fasting hyperhomocysteinemia, 5.1 (95%CI: 3.0 to 8.6) for factor V Leiden and 1.8 (95%CI: 0.7 to 4.2) for prothrombin G20210A. We found 14 patients and 3 controls with both hyperhomocysteinemia and factor V Leiden, which yielded an odds ratio of 11.6 (95%CI: 3.2 to 42.5). We found no interaction between hyperhomocysteinemia and prothrombin G20210A. The relative risk for MTHFR 677CT was 1.6 (95%CI: 1.1 to 2.4) and for MTHFR 677TT was 1.4 (95%CI: 0.7 to 2.8). The combined risk for MTHFR 677TT and factor V Leiden was 18.7 (95%CI: 3.3 to 108).

We conclude that hyperhomocysteinemia and factor V Leiden are risk factors for recurrent venous thrombosis. The risk of thrombosis appeared high for individuals who had both risk factors.

Keywords

Homocysteine - venous thrombosis - factor V Leiden - prothrombin G20210A - MTHFR
 

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