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

Author(s)

Orikaza, Cristina M. ^[1] ; Morelli, Vania M. ^[1] ; Matos, Marinez F. ^[1] ; Lourenco, Dayse M. ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Hematol & Hemotherapy Div, BR-04037000 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: THROMBOSIS RESEARCH; v. 133, n. 1, p. 120-124, JAN 2014.
• Web of Science Citations: 3

Abstract

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 Ltd. All rights reserved. (AU)

• FAPESP's process: 07/03109-2 - Role of gene polymorphisms related to hemostasis and estrogen receptors as risk factors for venous cerebral thrombosis
• Grantee: Dayse Maria Lourenco
• Support Opportunities: Regular Research Grants