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.
