title: The role of point mutations in the genes, predisposing inherited thrombophilia in the pathogeneses of proximal and distal deep vein thrombosis in Georgian population.
abstract: Duration of treatment of venous thromboembolism (VTE) and prevention of its recurrence represent significant problems of contemporary medicine, as the basic method of treatment - anticoagulation is frequently complicated by hemorrhage. Therefore, its duration is strictly defined and depends on existence of risk factors related to recurrence of thrombosis. Purpose of the conducted study was to establish the role of point mutations of prothrombin (PHG) - 20210G/A; Factor V Leiden (FVL) - 1691G/A and methylenetetrahydrofolate reductase (MTHFR) - 677C/T genes, i.e. inherited thrombophilia in the pathogenesis of proximal and distal lower extremity deep vein thrombosis in patients of the Georgian population, as in case of proximal thrombosis there is a higher risk of recurrent thrombosis. The above mutations were detected by PCR and single nucleotide primer extension reaction, followed by Enzyme Linked Immuno-Sorbent Assay (ELISA) in 61 patients with venous thromboembolism of various localizations, out of which: 49 patients were diagnosed with unprovoked proximal thromboembolism confirmed by objective studies and 12 patients were diagnosed with distal thromboembolism. The difference between the groups was evaluated by F (Fisher) precise criterion. According to statistical analysis of the results, incidence of FVL mutation in the group of patients with proximal thrombosis was significantly higher compared to patients with distal thrombosis 0.43 and 0.08 (p=0.0256), respectively. Similar tendencies were observed in case of carriage of prothrombin gene and MTHFR gene mutations, as their presence was higher in the group of patients having proximal thrombosis than in patients with distal thrombosis, however, this difference was not found to be statistically significant. It should be particularly mentioned that double or triple heterozygous or homozygous carriage of studied mutations with various options was confirmed in 15 of 61 patients and the above genotypes were observed only in the group of patients having proximal thrombosis. According to the results obtained from this investigation, it is possible to consider inherited thrombophilia, especially Leiden mutation and double or triple heterozygous and homozygous carriage of studied mutations in the Georgian population as an independent risk factor of development of proximal thrombosis, which on its part, represents one of the risk factors of development of recurrent thrombosis and conduct proper long-standing anticoagulation therapy and take secondary preventive measures in patients of similar genotype to reduce the risk of recurrent thrombosis.
authors.affiliation: Forensic Biology (DNA) Department, National Forensics Bureau; Institute of Hematology and Transfusiology; The Centre of Vascular and Heart Diseases, Tbilisi, Georgia.
authors.forename: N
authors.initials: N
authors.lastname: Pirtskhelani
authors.affiliation: Forensic Biology (DNA) Department, National Forensics Bureau; Institute of Hematology and Transfusiology; The Centre of Vascular and Heart Diseases, Tbilisi, Georgia.
authors.forename: N
authors.initials: N
authors.lastname: Kochiashvili
authors.affiliation: Forensic Biology (DNA) Department, National Forensics Bureau; Institute of Hematology and Transfusiology; The Centre of Vascular and Heart Diseases, Tbilisi, Georgia.
authors.forename: L
authors.initials: L
authors.lastname: Makhaldiani
authors.affiliation: Forensic Biology (DNA) Department, National Forensics Bureau; Institute of Hematology and Transfusiology; The Centre of Vascular and Heart Diseases, Tbilisi, Georgia.
authors.forename: N
authors.initials: N
authors.lastname: Pargalava
authors.affiliation: Forensic Biology (DNA) Department, National Forensics Bureau; Institute of Hematology and Transfusiology; The Centre of Vascular and Heart Diseases, Tbilisi, Georgia.
authors.forename: E
authors.initials: E
authors.lastname: Gaprindashvili
authors.affiliation: Forensic Biology (DNA) Department, National Forensics Bureau; Institute of Hematology and Transfusiology; The Centre of Vascular and Heart Diseases, Tbilisi, Georgia.
authors.forename: K
authors.initials: K
authors.lastname: Kartvelishvili
mesh_terms: D000293:Adolescent; D000328:Adult; D005165:Factor V / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005846:Georgia (Republic); D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D017354:Point Mutation; D011153:Population / Q000235:genetics; D011516:Prothrombin / Q000235:genetics*; D012307:Risk Factors; D019851:Thrombophilia / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D020246:Venous Thrombosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
chemical_list: C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)