A PROTHROMBIN GENE MUTATION IS SIGNIFICANTLY ASSOCIATED WITH VENOUS THROMBOSIS

This case-control study examined the prevalence of a prothrombin gene mutation in the 3'-untranslated region (UTR) first reported by Poort e t al in Dutch subjects with a history of venous thrombosis and in matc hed control subjects without a history of thrombosis. We tested the hy pothesis that the presence of the 3'UTR prothrombin mutation would con vey a higher risk of venous or arterial thrombosis and therefore would be found in a higher-than-normal percentage of subjects with a histor y of thrombosis. Our study included 100 subjects: 50 with a history of thrombosis (21 with venous thrombosis and 29 with arterial thrombosis , who had been recruited from an anticoagulation clinic) and 50 contro l subjects without a history of thrombosis. DNA from these subjects wa s analyzed by polymerase chain reaction and agarose gel electrophoresi s. We found a statistically significant increase in the prevalence of the 3'UTR mutation in subjects with a history of venous thrombosis com pared with subjects without thrombosis. The prevalence of the 3'UTR pr othrombin mutation was 19% (4/21; 3 heterozygous and 1 homozygous) in subjects with a history of venous thrombosis, 0% (0/29) in subjects wi th a history of arterial thrombosis, and 2% (1/50) in control subjects (P<.0245, by Fisher's exact test for comparison of subjects with vers us those without a history of venous thrombosis). The G-->A mutation a t nucleotide 20 210 in the 3'UTR was confirmed by direct DNA sequencin g. The similar increased prevalence of the 3'UTR mutation in subjects with venous thrombosis in our population and in the Dutch population s tudied by Poort et al suggests that this mutation is an important risk factor for venous thrombosis in the general white population.