Thrombophilic Gene Mutations in Relation to Different Manifestations of Venous Thromboembolism: A Single Tertiary Center Study

Background: Venous thromboembolism (VTE) is a common and potentially lethal disorder that manifests mainly as deep vein thrombosis (DVT) of the extremities or pulmonary embolism (PE) and occurs as a consequence of genetic and environmental risk factors. We aimed to assess the role of inherited thrombophilia as a causative or additive factor in the development of VTE.Methods: The study included 310 patients (female: 154; mean age: 52.3 ± 16.9 years) with a first episode of VTE and 289 age- and sex-matched healthy controls. All participants underwent screening for thrombophilia-associated polymorphisms including factor V Leiden (FVL), prothrombin G20210A (PTG), factor V H1299 R (factor V HR2), factor XIII V34 L, β-fibrinogen-455 G>A, plasminogen activator inhibitor-1 4G/5G, human platelet antigen-1 a/b, methylene tetrahydrofolate reductase (MTHFR) C677 T, MTHFR A1298C, angiotensin-converting enzyme I/D, apolipoprotein B R3500Q, and apolipoprotein E (Apo E). In addition, serum homocysteine (Hcy) levels were measured.Results: In the patient group, 247 (80%) had isolated DVT, 43 (14%) had DVT plus PE, and 20 (6%) had isolated PE. The mean Hcy levels were similar in VTE subgroups and controls. Compared to controls, patients with isolated DVT, DVT plus PE, and isolated PE showed significantly higher frequencies for the following—heterozygous FVL mutation, isolated DVT (28.3%), DVT plus PE (44.2%), isolated PE (50%), controls (8.3%; P < .001); heterozygous PTG mutation, isolated DVT (11.3%), DVT plus PE (20.9%), isolated PE (25%), controls (5.9%; P < .01); Apo E 2/4, isolated DVT (9.7%), DVT plus PE (9.3%), isolated PE (5%), controls (1%; P < .01).The MTHFR A1298C mutation showed a significantly higher frequency in isolated patients with PE than in those with isolated DVT ( P = .006) and in controls ( P = .008). The frequencies of other genetic mutations or polymorphisms showed similar frequencies in all comparisons. In logistic regression analysis, heterozygous FVL mutation was the only independent predictor of VTE (odds ratio: 3.9, 95% confidence interval: 1.3-11.2; P = .012).Conclusion: Except than FVL, PTG, and Apo E 2/4 mutations, many of aforementioned thrombophilic factors known to be associated with VTE did not demonstrate any relationship with VTE. Heterozygous mutation of FVL was an independent predictor for VTE.