Haplotypes of TAFI gene and the risk of cerebral venous thrombosis - a case-control study

• Autor(a) principal: Orikaza, Cristina M. [UNIFESP]
• Data de Publicação: 2014
• Outros Autores: Morelli, Vania M. [UNIFESP], Matos, Marinez Farana [UNIFESP], Lourenco, Dayse M. [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1016/j.thromres.2013.10.040; http://repositorio.unifesp.br/handle/11600/37119
• topic: Cerebral venous thrombosis; Venous thromboembolism; Thrombin activatable fibrinolysis inhibitor; Single nucleotide polymorphisms; Haplotypes

Introduction: Cerebral venous thrombosis (CVT) is an uncommon disease with some differences compared to other-site thrombosis, including a higher frequency in young people, female sex and oral contraceptive users. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a regulator of fibrinolysis, whose levels are genetically controlled and its increase is associated to thrombosis. Our objective was to investigate in a case-control study the association between CVT and TAFI single nucleotide polymorphisms (SNPs) and its haplotypes in comparison to other-site venous thrombosis and controls.Materials and Methods: Seventy two patients with CVT were compared to 143 individuals with no history of thromboembolic events (control group) and to 128 patients with deep vein thrombosis in the limbs and/or pulmonary embolism(venous thromboembolism-VTE group). SNPs were genotyped by restriction fragment length polymorphism or allele-specific PCR for F2 20210G > A, F5 1691G > A, TAFI (-1053C > T, -438G > A, 505G > A, 1040C > T and + 1542C > G).Results: the GTC haplotype for TAFI 505G > A/1040C > T/+ 1542C > G SNPs was associated with an increased risk of CVT compared to controls [odds ratio (OR) 2.67, 95% confidence interval (CI): 1.13 - 6.34) and VTE group (OR 2.51, 95%CI: 1.07 - 8.06). the CVT risk became even more pronounced when evaluating unprovoked or hormone-related thrombosis cases: CVT compared to controls (OR 3.24, 95%CI: 1.19 - 8.82) and VTE group (OR 4.32, 95%CI: 1.27 - 14.63).Conclusions: Our data indicate that the GTC haplotype for TAFI 505G > A/1040C > T/+ 1542C > G SNPs increased the risk of CVT in comparison to controls and VTE cases. Further studies are required to confirm our findings. (C) 2013 Elsevier B.V. All rights reserved.