Prevalence of the Prothrombin Gene Variant (nt20210A) in Venous Thrombosis and Arterial Disease

a b s t r a c tPolymorphisms of genes encoding key factors for the control and activation of inflammatory response and coagulation cascade regulation may play a role in genetic susceptibility to acute myocardial infarction (AMI). This study sought to analyze the effect of TNF À308G/A and pro-thrombin (FII) 20210G/A polymorphisms on the laboratory parameters of young patients affected by AMI. Results indicated that TNF À308A positive genotype frequencies were increased in these patients and that a genetically determined higher production of TNF-a is associated in young subjects to a more severe cardiac damage as depicted by higher levels of troponin, Creatine kinase-MB Isoenzyme (mCK-MB) and a significant increased plasma fibrinogen levels. Similar and probably additive effects on might have a genetically determined increased production of pro-thrombin even if no significant differences in genotype frequencies of pro-thrombin (FII) 20210G/A polymorphisms were observed in this study. All together these results, indicating the relationship among genetically determined TNFa and FII production and increased levels of tissue damage markers of AMI, suggest that a complex genetic background, might be involved in susceptibility to AMI in young men influencing the extension and severity of the disease.

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“…Several studies confirmed this initial observation both in venous thrombosis and arterial disease [30,32].…”

Section: Introductionsupporting

confidence: 55%

Myocardial infarction marker levels are influenced by prothrombin and tumor necrosis factor-α gene polymorphisms in young patients

et al. 2013

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“…Both these abnormalities are commonly found in patients with venous thromboembolism, with prevalences varying between 20% and 50% for factor V Leiden (Griffin et al, 1993;Koster et al, 1993;Svensson & Dahlba Èck, 1994) and between 5% and 19% for the prothrombin gene mutation (Poort et al, 1996;Arruda et al, 1997;Brown et al, 1997;Hillarp et al, 1997;Kapur et al, 1997;Cattaneo et al, 1998;Leroyer et al, 1998;Margaglione et al, 1998), depending on the criteria used for patients' selection. Their frequency in general populations of Caucasian origin varies from 1% to 7% for factor V Leiden (Rees et al, 1995) and from 1% to 5% for the prothrombin gene mutation (Rosendaal et al, 1998).…”

mentioning

confidence: 99%

The risk of venous thromboembolism in family members with mutations in the genes of factor V or prothrombin or both

et al. 2000

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Summary. Factor V Leiden and the G20210A mutation in the prothrombin gene are the most frequent abnormalities associated with venous thromboembolism. It is unknown whether the risks due to the presence of either mutation are of the same magnitude. We compared the prevalence and incidence rate of venous thromboembolism in relatives with either mutation or both. The finding of different rates might influence the strategies for primary prevention of thrombosis in carriers of these mutations. The study population included 1076 relatives of probands with the prothrombin gene mutation, factor V Leiden or both who underwent screening for inherited thrombophilia and were found to be carriers of single mutations or double mutations or who were non-carriers. The prevalence of venous thromboembolism was 5´7% in relatives with the prothrombin gene mutation, 7´8% in those with factor V Leiden, 17´1% in those with both mutations and 2´5% in non-carriers. Annual incidences of thrombosis were 0´13% [95% confidence interval (CI) 0´06±0´24], 0´19% (0´13±0´25), 0´42% (0´15±0´83) and 0´066% (0´03±0´11), respectively, and the relative risk of thrombosis was two times higher in carriers of the prothrombin gene mutation, three times higher in those with factor V Leiden and six times higher in double carriers than in non-carriers. The incidence of venous thromboembolism in carriers of the prothrombin gene mutation is slightly lower than that observed in carriers of factor V Leiden, whereas in carriers of both mutations it is two or three times higher. These findings suggest that lifelong primary anticoagulant prophylaxis of venous thromboembolism is not needed in asymptomatic carriers of single or double mutations. Anticoagulant prophylaxis seems to be indicated only when transient risk factors for thrombosis coexist with mutations.

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“…The association of factor II G20210A mutation with an increased risk of venous thrombosis was reported by Poort et al [16]. Several studies confirmed this initial observation [17,18]. The patients with this genetic change show increased prothrombin levels and therefore more thrombotic activity [19].…”

Section: Other Genes In Coagulation Cascadementioning

confidence: 67%

Pharmacogenetic Aspects of Coumarinic Oral Anticoagulant Therapies

et al. 2011

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Coumarinic oral-anticoagulants (COAs) are commonly used for treatment of thromboembolic events. However, these medications have a narrow therapeutic range and there are large inter-individual variations in drug response. This is especially important in the initial phases of oral-anticoagulant therapy. Recent advancements in pharmacogenetics have established that clinical outcomes in oral-anticoagulant therapy are affected by genetic factors. The allelic variants of genes like cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) are closely associated with maintenance dose of oral anti-coagulants. In addition, GGCX (Gammaglutamyl carboxylase) polymorphism at position 12970 (rs11676382), CYP4F2 (rs2108622; V433M; 1347 C [ T) and Apolipoprotein E (APOE) variants have been shown to explain a small but significant influence on dose requirements. There are large differences in the frequencies of these polymorphisms between different world populations which are also related to the requirements of oral anticoagulants. However, the final drug dosage in an individual is determined by complex sets of genetic and environmental factors and several dosing algorithms which combine clinical and genetic parameters to predict therapeutic COA doses have also been developed. The algorithm based dose prediction shows the importance of pharmacogenetic testing in patients undergoing oral anticoagulant therapies.

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Prevalence of the Prothrombin Gene Variant (nt20210A) in Venous Thrombosis and Arterial Disease

Cited by 168 publications

References 15 publications

Myocardial infarction marker levels are influenced by prothrombin and tumor necrosis factor-α gene polymorphisms in young patients

Myocardial infarction marker levels are influenced by prothrombin and tumor necrosis factor-α gene polymorphisms in young patients

The risk of venous thromboembolism in family members with mutations in the genes of factor V or prothrombin or both

Pharmacogenetic Aspects of Coumarinic Oral Anticoagulant Therapies

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