Identification of polymorphisms in the 5'-untranslated region of the TAFI gene: relationship with plasma TAFI levels and risk of venous thrombosis

• Published in: Haematologica (Roma) Vol. 86; no. 5; pp. 510 - 517
• Main Authors: Franco, RF, Fagundes, MG, Meijers, JC, Reitsma, PH, Lourenco, D, Morelli, V, Maffei, FH, Ferrari, IC, Piccinato, CE, Silva, WA, Jr, Zago, MA
• Format: Journal Article
• Language: English
• Published: Pavia Haematologica 01-05-2001
• Subjects: 5' Untranslated Regions - genetics; Adolescent; Adult; Aged; Biological and medical sciences; Brazil - epidemiology; Carboxypeptidase B2 - adverse effects; Carboxypeptidase B2 - blood; Carboxypeptidase B2 - genetics; Case-Control Studies; Child; Child, Preschool; Female; Genotype; Hematologic and hematopoietic diseases; Humans; Male; Medical sciences; Middle Aged; Platelet diseases and coagulopathies; Polymorphism, Genetic; Risk Factors; Sequence Analysis, DNA; Venous Thrombosis - epidemiology; Venous Thrombosis - etiology; Venous Thrombosis - genetics; Brazil; Human; Serine endopeptidases; Enzyme; Cardiovascular disease; Thrombin; Epidemiology; Fibrinolysis; Thrombosis; Venous disease; Vascular disease; Peptidases; Gene; Risk factor; Genetics; Hydrolases; Inhibitor; Deep vein; Mutation; Polymorphism
• ISSN: 0390-6078; 1592-8721

Laboratory of Hematology, Department of Clinical Medicine, School of Medicine of Ribeirao Preto, University of Sao Paulo, 14048-900, Ribeirao Preto, SP, Brazil. [e-mail]
BACKGROUND AND OBJECTIVES. Thrombin activatable fibrinolysis inhibitor (TAFI) plays an important role in hemostasis, functioning as a potent fibrinolysis inhibitor. TAFI gene variations may contribute to plasma TAFI levels and thrombotic risk. DESIGN AND METHODS. We sequenced a 2083-bp region of the 5'-regulatory region of the TAFI gene in 127 healthy subjects searching for variations, and correlated identified polymorphisms with plasma TAFI levels. TAFI polymorphisms were examined as risk factors for venous thrombosis by determining their prevalence in 388 patients with deep venous thrombosis (DVT) and in 388 controls. RESULTS. Seven novel polymorphisms were identified: -152 A/G, -438 A/G, -530 C/T, -1053 T/C, -1102 T/G, -1690 G/A, and -1925 T/C. -152 A/G, -530 C/T and -1925 T/C were found to be in strong linkage disequilibrium, as were the -438 A/G, -1053 T/C, -1102 T/G and -1690 G/A. Plasma TAFI levels were higher in -438GG/-1053CC/-1102GG/-1690AA homozygotes than in -438AG/-1053TC/-1102TG/-1690GA heterozygotes, and -438AA/-1053TT/-1102TT/-1690GG homozygotes had the lowest TAFI levels (p=0.0003). TAFI concentrations in -152AA/-530CC/-1925TT homozygotes were somewhat higher but not significantly different from levels observed for -152AG/-530CT/-1925TC heterozygotes. Taken in combination, -438AG/-1053TC/-1102TG/-1690GA and -438AA/-1053TT/-1102TT/-1690GG yielded an OR for DVT of 0.8 (95%CI: 0.6-1). In subjects aged