title: Polymorphism G-308A in the promoter of the tumor necrosis factor-α gene and its association with the risk of venous thromboembolism.
abstract: 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 α (TNF-α) is associated with an increased transcription activity of this gene, increased TNF-α 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-α 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.
authors.affiliation: Department of Human Pharmacology and Toxicology, University of Veterinary and Pharmaceutical Sciences Brno, The Czech Republic. kristynahorak@gmail.com
authors.forename: Kristyna
authors.initials: K
authors.lastname: Horakova
authors.forename: Alicja
authors.initials: A
authors.lastname: Chylkova
authors.forename: Michal
authors.initials: M
authors.lastname: Kolorz
authors.forename: Ladislava
authors.initials: L
authors.lastname: Bartosova
authors.forename: Vaclav
authors.initials: V
authors.lastname: Pechacek
authors.forename: David
authors.initials: D
authors.lastname: Starostka
authors.forename: Katerina
authors.initials: K
authors.lastname: Wroblova
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005165:Factor V / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D054556:Venous Thromboembolism / Q000235:genetics; D020246:Venous Thrombosis / Q000235:genetics*; D055815:Young Adult
chemical_list: D014409:Tumor Necrosis Factor-alpha; C095381:factor V Leiden; D005165:Factor V