No interaction between factor V Leiden and hyperhomocysteinemia or MTHFR 677TT genotype in venous thrombosis

Miranda B. A. J. Keijzer; George F. Borm; Henk J. Blom; Gerard M. J. Bos; Frits R. Rosendaal; Martin den Heijer

doi:10.1160/TH06-09-0486

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 97(01): 32-37
DOI: 10.1160/TH06-09-0486

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

No interaction between factor V Leiden and hyperhomocysteinemia or MTHFR 677TT genotype in venous thrombosis

Results of a meta-analysis of published studies and a large case-only study

Miranda B. A. J. Keijzer

¹Department of Endocrinology

,

George F. Borm

²Department of Epidemiology and Biostatistics

,

Henk J. Blom

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

,

Gerard M. J. Bos

⁴Department of Hematology, University Hospital Maastricht

,

Frits R. Rosendaal

⁵Thrombosis and Haemostasis Research Center, Leiden University Medical Center, Leiden; The Netherlands

,

Martin den Heijer

¹Department of Endocrinology

²Department of Epidemiology and Biostatistics

› Author Affiliations

Abstract

Summary

Homocysteine may have a thrombogenic effect through inhibition of inactivation of factor Va by activated protein C. Because factor V Leiden also leads to resistance of factor V to activated protein C, it would be possible that both factors show interaction for the risk of venous thrombosis. This has been reported in some studies, but not in others. We performed a meta-analysis to investigate a possible interaction between factor V Leiden and hyperhomocysteinemia, including 825 subjects with venous thrombosis and 2,109 controls, for the risk of venous thrombosis. In addition, we assessed a possible interaction between factor V Leiden and MTHFR 677TT genotype (the most common genetic determinant of homocysteine levels), including 2,547 subjects with venous thrombosis and 4,327 controls. We also investigated the interaction effect of factor V Leiden and hyperhomocysteinemia in a large case-only study using data of the VITRO study, including 2,077 subjects with first-time venous thrombosis. The meta-analysis yielded no evidence for additive or multiplicative interaction between factor V Leiden and hyperhomocysteinemia [relative excess risk due to interaction (RERI) –1.77 (95%CI –8.61 to 5.08) and multiplicative interaction term 0.86 (95%CI 0.35 to 2.14)].The case-only study also showed no interaction effect [0.58 (95%CI 0.29 to 1.16)]. Also the metaanalysis on factor V Leiden and MTHFR 677TT yielded no evidence of interaction; RERI 0.13 (95%CI –3.60 to 3.86) and multiplicative interaction term 1.23 (95%CI 0.72 to 2.11). Both the meta-analyses of published studies and a large case-only study did not show evidence for interaction between factor V Leiden and hyperhomocysteinemia for risk of venous thrombosis.

Keywords

MTHFR - Methylenetetrahydrofolatereductase - homocysteine - factor V Leiden - meta-analysis - case-only - case-control - VITRO

Full Text

References

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