Genetic Risk Factors of Venous Thromboembolism in the East Algerian Population

Abstract

Many genetic risk factors have been identified for causing venous thromboembolism (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. In this case-control study, we aimed to determine the frequency of prothrombin G20210A and factor V Leiden (FVL) G1691A polymorphisms and protein C, protein S, and antithrombin III deficiencies in the East Algerian population and to investigate whether these genetic factors are associated with VTE. On the other hand, our study tends to evaluate the status of JAK2V617F and calreticulin (CALR) mutations among these cases. The participants consisted of 121 cases with VTE and 146 healthy controls. Polymorphisms of FVL G1691A and prothrombin G20210A were genotyped by polymerase chain reaction (PCR) restriction fragment length polymorphism. JAK2-V617F and calreticulin mutations were analyzed by quantitative PCR and PCR followed by capillary electrophoresis sequencing, respectively. Protein C, protein S, and antithrombin levels were determined and then hereditary deficiencies were identified. Of all cases and controls, none was a carrier of the antithrombin III deficiency, prothrombin gene G20210A, and CALR mutations. Only 1 case reported having a positive JAK2 mutation (mutant allele burden was 15%). The FVL mutation (GA/AA) was found in 14 (11.6%) cases and 2 (1.4%) controls and it was significantly different between both the groups ( P = .001). Deficiencies of protein S and protein C were detected in 17 (18.8%) cases. The univariate analysis resulted in a significant impact of FVL (odds ratio [OR] = 9.4, 95% confidence interval [CI] = 2.1-42.3; P = .003) and of protein S deficiency (OR = 16.9, 95% CI =2.1-132.8, P = .007) on the VTE status. Both factors stayed significant after adjustment for sex and age. The OR of the protein C deficiency was slightly elevated (OR = 6.4, 95% CI = 0.7-55.5), but it did not reach the level of statistical significance ( P = .091), and it was therefore not considered as a risk factor. In conclusion, coagulant factor V gene G1691A mutation and protein S deficiency constitute important genetic risk factors in patients with VTE in Eastern Algeria. The somatic mutation of JAK2 V617F and CALR mutations are less frequent causes of VTE, thus routine testing for these mutations is not recommended.

Prevalence and phenotypes of JAK2 V617F and calreticulin mutations in a Danish general population

“…3 JAK2 V617F has also been detected in healthy volunteers 4,5 and patients with cardiovascular diseases, 6 venous thromboses, 7 splanchnic vein thromboses, 8 and apoplexias, 9 all vascular complications associated with MPN. Few studies have assessed CALR in other disease entities, [9][10][11][12][13][14][15] with only rare detection of CALR in patients with splanchnic vein thrombosis 14 and cerebral venous thrombosis. 15 JAK2 V617F is also more prevalent among smokers, 16 and smoking has been suggested to be a risk factor for MPN development [17][18][19][20][21] and other related myeloid neoplasias [22][23][24] due to the chronic inflammatory stimulus.…”

Diagnostic challenge of the newborn patients with heritable protein C deficiency

“…The genetic risk of venous thromboembolism is increased in subjects with protein C (PC), protein S (PS) and antithrombin (AT) deficiencies, and modestly increased in those with factor V G1691A (FVL) and prothrombin G20210A (FII) variants [7, 8]. The allele frequency of FVL or FII variant shapes the landscape of molecular epidemiology for inherited thrombosis in Caucasians [9–11]. By contrast, the absence of FVL or FII variant in East Asia raises the clinical impact of PC, PS, and AT deficiency on thromboembolism in Asian patients [12–14].…”

Investigation of the Influence of Thrombophilic Genes Polymorphism, Including Serpin 1 (Pai-I), Fii, Prothrombin and Itgb3-Β Integrin, on the Frequency of Stroke in Association With Controllable Risk Factors for Its Occurrence

“…This means that an increased risk of thrombophilia occurs even in a heterozygous form of polymorphism (G / A). The presence of the 20210G> A polymorphism of the prothrombin gene in a homozygous or heterozygous form significantly (in 3 and more times, and against the background of smoking -40 and more times) increases the risk of venous thrombosis, including thrombosis of the vessels of the brain and heart, especially at younger ages [21,22].…”