title: The impact of single nucleotide polymorphisms of the thrombin activatable fibrinolysis inhibitor (TAFI) gene on TAFI antigen levels in healthy children and pediatric oncology patients.
abstract: The thrombin activatable fibrinolysis inhibitor (TAFI) influences the pathways regulating fibrin formation and deposition. The enormous TAFI plasma level variability present in adults may be explained by a combination of two polymorphisms in the TAFI gene (+1542C>G; 505G>A). We aimed to correlate these two polymorphisms with plasma TAFI antigen concentrations in healthy children and pediatric oncology patients with and without venous thrombosis who were supplied with Broviac central venous catheters. Polymorphisms were detected by restriction fragment length polymorphism (RFLP) analysis of polymerase chain reaction (PCR) amplification, whereas TAFI concentration was determined using a commercial enzyme-linked immunosorbent assay (ELISA). Samples from 57 controls and 67 pediatric patients (11 venous thrombotic complications) were studied. TAFI levels in healthy children and patients were not influenced by gender or age. Compared with the 505GG carriers (wild type), 505AA carriers as well as heterozygous 505GA carriers each exhibited significantly higher TAFI antigen concentrations. In contrast, the lowest TAFI levels were detected in homozygous carriers of the +1542GG polymorphism. A combination of the genotype 505AA (homozygous carrier) and +1542CC (wild type) was present in 13 probands and resulted in the highest TAFI levels. Although in oncologic patients the risk of thrombosis was markedly increased by the heterozygous factor V 1691G>A mutation, the two TAFI polymorphisms investigated exerted no thrombogenic influence.
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital of Technical University, Dresden, Germany. ralf.knoefler@mailbox.tu-dresden.de
authors.forename: Ralf
authors.initials: R
authors.lastname: Knoefler
authors.forename: Kathrin
authors.initials: K
authors.lastname: Ludwig
authors.forename: Heike
authors.initials: H
authors.lastname: Kostka
authors.forename: Eberhard
authors.initials: E
authors.lastname: Kuhlisch
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siegert
authors.forename: Meinolf
authors.initials: M
authors.lastname: Suttorp
mesh_terms: D000367:Age Factors; D000941:Antigens / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005165:Factor V / Q000235:genetics; D005260:Female; D005337:Fibrin / Q000378:metabolism; D051548:Histone Acetyltransferases; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics; D008297:Male; D009369:Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012016:Reference Values; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics* / Q000276:immunology; D035362:Transcription Factor TFIID / Q000235:genetics* / Q000276:immunology
chemical_list: D000941:Antigens; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D005165:Factor V; D005337:Fibrin; D051548:Histone Acetyltransferases; C069001:TATA-binding protein associated factor 250 kDa