Genetic risk factors in patients with deep venous thrombosis, a retrospective case control study on Iranian population

Abstract

BackgroundVenous thromboembolism (VTE) could be manifested as deep venous thrombosis (DVT) or pulmonary embolism (PE). DVT is usually the more common manifestation and is usually formation of a thrombus in the deep veins of lower extremities. DVT could occur without known underlying cause (idiopathic thrombosis) which could be a consequence of an inherited underlying risk factor or could be a consequence of provoking events, such as trauma, surgery or acute illness (provoked thrombosis). Our aim in this study was to assess the impact of some previously reported genetic risk factors including, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, plasminogen activator inhibitor-1(PAI-1) 4G/5G, prothrombin 20210 and FV Leiden on occurrence of DVT in a population of Iranian patients.MethodsThis long-term study was conducted on 182 patients with DVT and also 250 age and sex matched healthy subjects as control group. The diagnosis of DVT was based on patient’s history, clinical findings, D-dimer test, and confirmed by Doppler ultrasonography. After confirmation of DVT, both groups were assessed for the five mentioned mutations. The relationship between mutations and predisposition to DVT was calculated by using logistic regression and expressed as an OR with a 95 % confidence interval (CI).ResultsOur results revealed that FV Leiden (OR 6.7; 95 % CI = 2.2 to 20.3; P = 0.001), MTHFR C677T (OR 6.0; 95 % CI = 2.2 to 16.4; P < 0.001), MTHFR A1298C (OR 8.3; 95 % CI = 4.4 to 15.8; P < 0.001), and PAI-1 4G/5G (OR 3.8; 95 % CI = 2.1 to 7.2; P < 0.001) mutations were all significantly associated with an increased risk of DVT. Prothrombin 20210 was found in none of the patients and controls.ConclusionOur findings suggest that genetic risk factors have a contributory role on occurrence of DVT.

MTHFR A1298C and C677T Polymorphisms Are Associated with Increased Risk of Venous Thromboembolism: A Retrospective Chart Review Study

“…Likewise, another meta-analysis involving approximately 120,000 cases and 180,000 controls found a significant 57% increased risk of VTE in C677T homozygotes compared with heterozygotes and wild-types, in a Chinese population, whereas in Caucasians no significant association was found [11]. The MTHFR A1298C polymorphism is less well characterized but also reported to lead to increased VTE risk in the Iranian population [12]. However, conflicting results exist, and hence the role of MTHFR polymorphism in VTE is still controversial.…”

Association between plasminogen activator inhibitor gene polymorphisms and osteonecrosis of the femoral head susceptibility

“…Thrombosis formation is influenced by PAI-1 gene polymorphisms. [ 24 ] Accumulating evidences have suggested that the PAI-1 gene 4G/5G polymorphism might be an etiological factor for ON occurrence in renal transplant patients, [ 25 ] post-SARS patients [ 26 ] and glucocorticoid-induced ON patients. [ 27 ] There also other polymorphisms exist in the PAI-1 gene, such as rs6092 (exon 1) and rs7242 (3′UTR).…”

Risk factors for venous thromboembolism in women

“…было обнаружено, что инфаркт миокарда, возможно, является независимым от других факторов риска предиктором ВТЭ [147]. Кроме того, недавно с помощью полногеномных исследований были обнаружены неизвестные ранее тромбогенные мутации, связанные не только с ВТЭ, но и с артериальными тромбозами [148,149]. В свою очередь, исследования Sumner и др.…”