Cristina M Orikaza1, Vânia M Morelli2, Marinez F Matos2, Dayse M Lourenço2. 1. Hematology and Hemotherapy Division, Federal University of Sao Paulo, SP, Brazil. Electronic address: cm.orikaza@unifesp.br. 2. Hematology and Hemotherapy Division, Federal University of Sao Paulo, SP, Brazil.
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.
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.
Authors: Yoshimasa Imoto; Atsushi Kato; Tetsuji Takabayashi; Whitney Stevens; James E Norton; Lydia A Suh; Roderick G Carter; Ava R Weibman; Kathryn E Hulse; Kathleen E Harris; Anju T Peters; Leslie C Grammer; Bruce K Tan; Kevin Welch; Stephanie Shintani-Smith; David B Conley; Robert C Kern; Shigeharu Fujieda; Robert P Schleimer Journal: J Allergy Clin Immunol Date: 2019-09-25 Impact factor: 10.793