Fine mapping of quantitative trait nucleotides underlying thrombin-activatable fibrinolysis inhibitor antigen levels by a transethnic study

• Published in: Blood Vol. 108; no. 5; pp. 1562 - 1568
• Main Authors: Frère, Corinne, Tregouet, David-Alexandre, Morange, Pierre-Emmanuel, Saut, Noémie, Kouassi, Dinar, Juhan-Vague, Irène, Tiret, Laurence, Alessi, Marie-Christine
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.09.2006; The Americain Society of Hematology
• Subjects: 3' Untranslated Regions - genetics; 5' Untranslated Regions - genetics; Adult; African Continental Ancestry Group - genetics; Biological and medical sciences; Blood coagulation. Blood cells; Blood Donors; Chromosome Mapping; Cote d'Ivoire; European Continental Ancestry Group - genetics; Female; France; Fundamental and applied biological sciences. Psychology; General aspects, investigation methods, hemostasis, fibrinolysis; Genotype; Histone Acetyltransferases; Humans; Linkage Disequilibrium; Male; Molecular and cellular biology; Polymorphism, Genetic; Quantitative Trait Loci; TATA-Binding Protein Associated Factors - blood; TATA-Binding Protein Associated Factors - genetics; Transcription Factor TFIID - blood; Transcription Factor TFIID - genetics; France; Cote d'Ivoire; Human; Cartography; Blood coagulation; Ethnic origin; Enzyme; Quantitative character; Phylogeny; Peptidases; Hydrolases; Carboxypeptidase U; Genetics; Metallocarboxypeptidases; Polymorphism; Thrombin activatable fibrinolysis inhibitor
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-01-008094

Recent studies revisiting the association between plasma thrombin-activatable fibrinolysis inhibitor (TAFI) Ag levels and polymorphisms of the CPB2 gene (coding for TAFI) suggested that TAFI Ag levels were influenced by 2 major quantitative trait nucleotides (QTNs) in European whites. However, the strong linkage disequilibrium (LD) between CPB2 polymorphisms in European whites did not allow one to distinguish which polymorphisms could be the putative QTNs. To get a better insight into the identification of QTNs, a transethnic haplotype analysis contrasting 2 populations of African and European subjects was performed using 13 CPB2 polymorphisms. Results of the haplotype analyses suggested that 3 QTNs had independent effects and explained about 15% of the TAFI variability, consistently in the 2 populations. The lower LD observed in the African population enabled us to identify the 1583T>A SNP located in 3′UTR as one of these QTNs, whereas the -2599C>G and -2345--2344insG SNPs located in the 5′ region might be the 2 other QTNs. A phylogenetic study suggested that these 3 polymorphisms occurred before the period of migration “out of Africa.” Although this transethnic comparison contributed to better map the putative CPB2 QTNs, further studies are required to clarify the role of the promoter region.