Etude des facteurs de risque génétiques de la maladie thromboembolique veineuse chez une population de l’Est-Algérien

Abstract

Venous thromboembolism (VTE) is a multifactorial disease in which the genetic component is important.Many genetic risk factors have been identified for causing VTE. Most of them affect the function of natural anticoagulant pathways, particularly the protein C system, although recent studies suggest a role of components of the hematopoietic pathway in the etiology of venous thrombosis. The aim of the study is to determine the risk of VTE associated with (prothrombin G20210A, factor V Leiden G1691A, MTHFR C677T) polymorphisms, (protein C, protein S, antithrombin III) deficiencies and hyperhomocysteinemia in a population of thrombotic patients compared to a control population. On the other hand, our study tends to evaluate the status of JAK2V617F and calreticulin mutations among thrombotic patients in eastern Algeria. Methods: 121 cases with VTE and 146 healthy controls were recruited in this study. Polymorphisms of FVL G1691A, prothrombin G20210A and MTHFR C677T were genotyped by PCR-RFLP. JAK2-V617F and calreticlin mutations were analysed by q-PCR and PCR followed by capillary electrophoresis sequencing respectively. The rate of coagulation inhibitors and tHcy levels were determined by Stago and immmulite 2000 instruments respectively; then hereditary deficiencies were identified. Results: Of all cases and controls, none was a carrier of the antithrombin III deficiency, prothrombin gene G20210A and calreticulin mutations. Only one case reported having a positive JAK2 mutation (mutant allele burden was 15%). The univariate analysis results in a significant association of the mutation (GA / AA) of factor V Leiden (OR = 9.4, 95% CI = 2.1, 42.3, P = 0.003) and protein S deficiency (OR = 16.9, 95% CI = 2.1; 132.8, P = 0.007) in VTE. The association remained significant even after adjustment for age and sex in the multivariate analysis. The odds ratio of protein C deficiency was slightly higher (OR = 6.4, 95% CI = 0.7, 55.5), however it is not statistically significant (P = 0.091). In addition, this study showed that there was no significant association between MTHFR C677T mutation, hyperhomocysteinemia and risk of venous thrombosis Conclusion: Our study supports the idea that the FV Leiden and protein S deficiency are independent prothrombotic risk factors in the population of eastern Algeria. The somatic mutation of JAK2 V617F and calreticulin are less frequent causes of VTE, thus routine testing for these mutations is not recommended.