Gene polymorphisms of tissue plasminogen activator and plasminogen activator inhibitor-1 in patients with antiphospholipid antibodies.
ABSTRACT Impaired fibrinolytical outcomes may be one of the pathogenic factors for thrombotic events in patients with antiphospholipid antibodies (aPL). We investigated the consequences of the gene polymorphisms of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) in patients positive for aPL.
Seventy-seven Japanese and 82 British patients with aPL were examined for Alu-repeat insertion (I)/deletion (D) polymorphism of the tPA gene by polymerase chain reaction (PCR), and 4G/5G polymorphism in the PAI-1 promoter gene by site-directed mutagenesis-PCR and restriction fragment length polymorphism analysis. Correlations between these polymorphisms and clinical symptoms of antiphospholipid syndrome (APS) (arterial thrombosis, venous thrombosis, miscarriage) were analyzed.
Significant differences in the allele frequencies of these genes did not exist between patients and controls. There was no significant correlation between these gene polymorphisms and clinical symptoms of APS in patients with aPL.
Polymorphisms of the tPA or PAI-1 genes probably do not significantly influence the risk of anerial thrombosis, venous thrombosis, or pregnancy morbidity in patients with aPL.
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ABSTRACT: Investigation of the clinical epidemiology of the antiphospholipid syndrome (APS) is in its early stages. During the past 20 years, studies of antiphospholipid antibodies (aPL) and APS have been made in many countries and ethno-geographical groups. aPL appear to occur in all populations studied, with some variations noted in their frequency and in the clinical complications. Environmental and genetic factors contribute to ethnic variation and susceptibility to APS and thus inter-ethnic differences in disease patterns may be due to environmental or genetic factors, or both.Annals of the Rheumatic Diseases 01/2006; 64(12):1671-6. · 9.11 Impact Factor
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ABSTRACT: Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent arterial or venous thrombosis or fetal loss and the presence of antiphospholipid antibodies (aPL). Genetic factors are thought to play a role in the susceptibility to APS. Similar to many other polygenic autoimmune diseases, human leukocyte antigen associations have been reported. The genetics of b(2)-glycoprotein I, one of the most representative target antigens of aPL, has been extensively studied. Additional genetic risk factors for the development of thrombosis in patients with aPL have also been discussed. However, the genes involved in APS have not been identified because antigen specificity of aPL and the pathophysiology of APS are highly heterogeneous and multifactorial. Genome-wide linkage analysis and larger cohort studies would lead to better understanding of the genes that might be involved in APS.Current Rheumatology Reports 01/2005; 6(6):458-62.
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ABSTRACT: The possibility of a genetic predisposition to develop antiphospholipid syndrome (APS) and to produce anticardiolipin antibodies and lupus anticoagulant has been addressed by family studies and population studies. Various studies suggest a familial occurrence of anticardiolipin antibodies and lupus anticoagulant, with or without clinical evidence of APS. This familial tendency could be genetically determined. Multiple human leucocyte antigen-DR or -DQ associations with antiphospholipid antibodies have been described. Genetic studies of a representative antigen, beta2-glycoprotein-I (beta(2)GPI), have been carried-out and a particular valine(247)/leucine polymorphism could be a genetic risk for presenting anti-beta(2)GPI antibodies and APS. Many other thrombosis-related genetic factors have been investigated in APS, but no additional risk for thrombosis has been indicated in affected patients. Although the mechanisms and pathophysiology of thrombosis in APS are highly heterogeneous and multifactorial, different genes and acquired factors seem to be involved. In this review, we will focus on those genetic variants that could contribute to the development of thrombosis in APS.British Journal of Haematology 08/2009; 147(3):289-96. · 4.94 Impact Factor