The risk of myocardial infarction in the presence of the Prothrombin 20210 mutation (AG genotype) was increased by 50% (odds ratio, 1.5; 95% confidence interval [95% CI], 0.6 to 3.8). The risk of myocardial infarction for carriership of factor V Leiden mutation was increased by 40% (odds ratio, 1.4; 95% CI, 0.8 to 2.2). When a coagulation defect was present (ie, the 20210 AG prothrombin genotype or the factor V Leiden mutation), the risk of myocardial infarction for carriers versus noncarriers was 1.4 (95% CI, 0.9 to 2.2). This risk was substantially increased when one of the major cardiovascular risk factors of smoking, hypertension, diabetes mellitus, or obesity also was present, with odds ratios varying between 3 and 6. These risks exceeded those of the single effects of the cardiovascular risk factors (ie, in the absence of the coagulation defect). CONCLUSIONS: We conclude that in men the 20210 G-->A variant of prothrombin is associated with an increased risk of myocardial infarction. The combined presence of major cardiovascular risk factors and carriership of a coagulation defect increases the risk considerably.

They suggest that being heterozygote for the allele variant 20210A of the prothrombin gene could be a genetic risk factor for developing myocardial infarction. The prevalence of heterozygotes for the prothrombin mutated allele was 3% among patients with myocardial infarction and 0.7% in the general population (P = 0.03). For individuals over 45 years old the prevalence among females was higher than among males (5% vs. 0%).

These data support the hypothesis that the prothrombin variant is a risk factor for venous thrombosis and suggest that it may also be a risk factor for arterial disease. The prevalence of 0.7% for 20210A allele in the control group increased to 4.3% (P = 0.021) among patients with venous thrombosis. There was also a high prevalence of the mutated allele in a selected arterial disease group (5.7%) without hyperlipoproteinemia, hypertension, and diabetes mellitus when compared to the controls (P = 0.013).

18% percent of the patients had the 20210 AG genotype, as compared with 1% of a group of healthy controls (100 subjects). The 20210 A allele was identified as a common allele (allele frequency, 1.2%; 95% confidence interval, 0.5% to 1.8%), which increased the risk of venous thrombosis almost threefold odds ratio, 2.8; 95% confidence interval, 1.4 to 5.6. The risk of thrombosis increased for all ages and both sexes. An association was found between the presence of the 20210 A allele and elevated prothrombin levels. Most individuals (87%) with the 20210 A allele are in the highest quartile of plasma prothrombin levels (> 1.15 U/mL). Elevated prothrombin itself also was found to be a risk factor for venous thrombosis.

5.5% were found to be heterozygous carriers of the 20210A allele vs. 1.2% in the control (allele frequency 0.61%, 95% CI 0.08-2.19). When patients with a known alternative hereditary risk factor for venous thrombosis (factor V Leiden mutation or deficiency of antithrombin, protein C or protein S) were excluded, the G20210A variant was found to increase the risk for venous thrombosis by approximately 5-fold (odds ratio 5.4, 95% CI 1.16-25.0). Patient size= 219

The prothrombin 20210GA genotype was nearly 5 times as prevalent (19/156 v 2/77; P < 0.02) in the symptomatic FVL carriers (odds ratio 5.21; 95% confidence interval 1.20-47.62), demonstrating that this important prothrombotic risk factor acts synergistically with FVL.

They have demonstrated that the prevalence of the PT 20210A allele is significantly greater in subjects with venous thrombosis and characterised heritable thrombophilia than in normal control subjects and that the additional inheritance of PT 20210A is associated with an increased risk of venous thromboembolism. They also confirmed that plasma prothrombin levels are significantly greater in subjects possessing the PT 20210A compared with those who do not. 8% of patients were heterozygous for the PT 20210A allele compared with 0.7% in the control subjects (p = 0.005). After exclusion of patients on warfarin, the mean plasma prothrombin of 113 subjects without 20210A was 1.09 U/ml, vs. 1.32 U/ml in 8 with the allele (p = 0.0002). Among the 101 patients with other risk factors (either factor V Leiden, protein S deficiency, protein C deficiency or antithrombin deficiency), the age adjusted mean number of venous thromboembolic episodes at diagnosis was 3.7 in those with the PT 20210A allele, as compared with 1.9 in those without (p = 0.0001).

Their results confirm the 20210 A allele of the prothrombin gene to be an important risk factor for venous thrombosis. The prevalence of the 20210 A allele was 7.1% (7/99) in the patient group, and 1.8% (5/282) in the healthy control group (p = 0.0095). The relative risk of venous thrombosis was calculated to be 4.2 (95% CI, 1.3 to 13.6), and was still significant when adjustment was made for age, sex and the factor V:R506Q mutation causing APC resistance [odds ratio 3.8 (95% CI, 1.1 to 13.2)]. 28% of the patients were carriers of the factor V:R506Q mutation. 34% (one patient carried both traits) of unselected patients with deep venous thrombosis were carriers of an inherited prothrombotic disorder.