title: Haplotypes of TAFI gene and the risk of cerebral venous thrombosis--a case-control study.
abstract: BACKGROUND
  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.
  
  
  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.affiliation: Hematology and Hemotherapy Division, Federal University of Sao Paulo, SP, Brazil. Electronic address: cm.orikaza@unifesp.br.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Orikaza
authors.affiliation: Hematology and Hemotherapy Division, Federal University of Sao Paulo, SP, Brazil.
authors.forename: Vânia M
authors.initials: VM
authors.lastname: Morelli
authors.affiliation: Hematology and Hemotherapy Division, Federal University of Sao Paulo, SP, Brazil.
authors.forename: Marinez F
authors.initials: MF
authors.lastname: Matos
authors.affiliation: Hematology and Hemotherapy Division, Federal University of Sao Paulo, SP, Brazil.
authors.forename: Dayse M
authors.initials: DM
authors.lastname: Lourenço
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D025901:Carboxypeptidase B2 / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D020767:Intracranial Thrombosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000235:genetics*; D055815:Young Adult
chemical_list: D025901:Carboxypeptidase B2
keywords: CI; CVT; Cerebral venous thrombosis; DVT; HRT; Haplotypes; LD; LOD; OC; OR; PCR; PE; RFLP; SNP; Single nucleotide polymorphisms; TAFI; Thrombin activatable fibrinolysis inhibitor; VTE; Venous thromboembolism; cerebral venous thrombosis; confidence interval; deep vein thrombosis; hormone replacement therapy; linkage disequilibrium; log odds disequilibrium; odds ratio; oral contraceptive; polymerase chain reaction; pulmonary embolism; restriction fragment length polymorphism; single nucleotide polymorphism; thrombin-activatable fibrinolysis inhibitor; venous thromboembolism