Polymorphism G-308A in the promoter of the tumor necrosis factor-α gene and its association with the risk of venous thromboembolism

The main abnormalities associated with the increased risk of venous thrombosis are the inherited deficiencies of antithrombin, protein C, protein S, the point mutations known as factor V Leiden and factor II G20210A. The association of other specific genes with thrombotic risk is less known. G-308A polymorphism in the promoter area of the gene coding for tumor necrosis factor alpha (TNF-alpha) is associated with an increased transcription activity of this gene, increased TNF-alpha production and subsequent predisposition to some illnesses. The aim of this work was to study the link between this polymorphism and predisposition to deep venous thrombosis (DVT). The research determined the frequency of the variant allele -308A in the gene for TNF-alpha in a group of 67 patients diagnosed with DVT and in a group of 62 healthy volunteers. We confirmed statistically significant link between the occurrence of the variant allele -308A and DVT (P=0.02). This mutation was associated with a 2.64-fold greater risk of venous thrombosis, 95% confidence interval (1.19-5.87). When excluding heterozygous and homozygous carriers of the Leiden mutation from both groups, the difference between the occurrence of the variant allele -308A in the groups of ill and healthy individuals remained statistically significant (P=0.04). The statistical significance was also confirmed after the exclusion of patients with mutation in the gene for prothrombin (P=0.02). The results of this work imply possible association between the variant allele -308A and the development of DVT. Blood Coagul Fibrinolysis 23: 316-319 (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.