Interaction between the G20210A mutation of the prothrombin gene and oral contraceptive use in deep vein thrombosis

Single-point mutations in the gene coding for prothrombin (factor II:A20210 ) or factor V (factor V:A1691) are associated with an increased risk of ven ous thromboembolism. The use of oral contraceptives is also a strong and in dependent risk factor for the disease, and the interaction between factor V :A1691 and oral contraceptives greatly increases the risk. No information i s available about the interaction between oral contraceptives and mutant pr othrombin. We investigated 148 women with a first, objectively confirmed ep isode of deep vein thrombosis and 277 healthy women as controls. Fourteen p atients (9.4%) were carriers of factor II:A202101 24 (16.2%) of factor V:A1 691, and 4 (2.7%) of both defects. Among controls, the prevalence was 2.5% for either factor II:A20210 or factor V:A1691, and there was no carrier of both the mutations. The relative risk of thrombosis was 6-fold for factor l n:A20210 and g-fold for factor V:A1691. The most prevalent circumstantial r isk factor in patients and the only one observed in controls was oral contr aceptive use, which per se conferred a 6-fold increased risk of thrombosis. The risk increased to 16.3 and 20.0 when women with factor II:A20210 or fa ctor V:A1691 who used oral contraceptives were compared with noncarriers an d nonusers. These figures indicate a multiplicative interaction between the genetic risk factors and oral contraceptives. No difference in the type of oral contraceptives was observed between patients and controls, those of t hird generation being the most frequently used (73% and 80%). We conclude t hat carriers of the prothrombin mutation who use oral contraceptives have a markedly increased risk of deep vein thrombosis, much higher than the risk conferred by either factor alone.