Institute of Rheumatology RAMS, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow, Russia

Hereditary factors such as factor V Leiden, G20210A prothrombin and C677T methylenetetrahydrofolate reductase (MTHFR) mutations are strongly associated with recurrent thrombotic events.
The association between antiphospholipid antibodies (aPL) and an increased risk of thrombosis is also well recognized.
The purpose of the present study is to analyze the interrelation between above genetic and acquired thrombotic risk factors in patients with antiphospholipid syndrome (APS) (secondary and primary) and systemic lupus erythematosus (SLE). 49 patients (mean age 37.6 ± 11.7 yrs, mean disease duration 23.5 ± 11.2 yrs) and 30 health individuals were included in this study.
The patients were divided into three groups: The first group (A) included 11 patients with SLE (ACR criteria, 1982), in the second group (B) was 23 patients with SLE + APS (criteria Harris E.N., Hughes GRW, 1986), the third group (C) consisted of 15 patients with primary APS (PAPS).
There were no differences in the age of patients in these groups but duration of disease was shorter in the groupe A. Anticardiolipin antibodies (aCL) and lupus anticoagulant as serological markers of APS were determined.
The aPL-related clinical manifestations such as thrombosis were estimated. Two PCR-based approaches, including restriction endonucleases and allele-specific primers, have been used for patient DNA screening for mutations. 22 of 49 (45%) patients were found to have mutations under study.
The frequency of C677T MTFHR mutation in patients and health individuals was approximately equal.
The heterozygous MTFHR mutation was found in 2 of 11 patients of group A, 9 mutations (7 heterozygous and 2 homozygous) were present in 23 subjects of group B, and 8 mutations (6 heterozygous and 2 homozygous) were found in 15 patients of group C, as well as 12 of 30 health individuals were found to be carriers of this mutation (10 heterozygous and 2 homozygous). No factor V Leiden and prothrombin gene mutations were identified in SLE patients, but 3 patients with SLE + APS and 3 individuals with PAPS were carriers of factor V Leiden.
Prothrombin mutation was found in 3 patients (1 patient with SLE + APS; 2 patients with PAPS). Thrombotic events occured in 24 patients with APS (10 primary and 14 secondary).
The number of thrombotic events in 22 carriers of mutations during the course of their disease were 64 against 26 cases in 17 thrombotic patients without mutations.
Four of 22 carriers of mutations were found to have double mutations: in two patients coexisted factor V Leiden and heterozygous C677T MTHFR and two of them had prothrombin mutation and C677T MTHFR.

Conclusion: The presence of some mutations in patients with APS associated with severe recurrent thrombotic complications.