The G1691 -> A mutation of factor V, but not the G20210 -> A mutation of factor II or the C677 -> T mutation of methylenetetrahydrofolate reductase genes, is associated with venous thrombosis in patients with lupus anticoagulants

Arterial and venous thrombosis are the most common manifestations of antiph ospholipid syndrome. To investigate whether genetic determinants contribute to their thrombotic risk, we studied the prevalence of the G1691 --> A mut ation in the gene coding for factor V, the G20110 --> A mutation in the pro thrombin gene and the C677 --> T mutation in the methylenetetrahydrofolate reductase gene in 152 patients with lupus anticoagulants. One hundred and t wenty-eight cases (84%) also had increased titres of anticardiolipin antibo dies. History of thrombosis was present in 96 patients (63%): 67 suffered f rom venous thrombosis only, 23 cases had arterial thrombosis only, six pati ents had both venous and arterial thrombosis. Five patients were heterozygo us for the G1691 --> A mutation in the factor V gene (3%). All of them (100 %) suffered from venous thrombosis compared with 68 out of the 147 cases wi thout the mutation (46%) (P = 0.0474). The prevalence of the G10210 --> A m utation in the prothrombin gene was evaluated in 145 patients; eight of the se patients were heterozygous (5%). Four of these patients (50%) experience d venous thrombosis compared with 65 out of the 137 patients without the mu tation (47%) (P = ns). Neither mutation was associated with arterial thromb otic events. No patient carried both mutations. The C677 --> T mutation in the methylenetetrahydrofolate reductase gene was assessed in 83 patients; 1 5 of them (18%) were homozygous and 37 (44%) were heterozygous. There was n o significant association between the status of the mutation and history of venous and arterial thrombosis, No significant correlation was found among the three groups. In conclusion, only the G1691 --> A mutation in the fact or V gene was associated with the thrombotic risk of patients with lupus an ticoagulants.