Quantification of thrombin activatable fibrinolysis inhibitor (TAFI) gene polymorphism effects on plasma levels of TAFI measured with assays insensitive to isoform-dependent artefact

Corinne Frère; Pierre Emmanuel Morange; Noémie Saut; David Alexandre Tregouet; Mariana Grosley; Jérôme Beltran; Irène Juhan-Vague; Marie-Christine Alessi

doi:10.1160/TH04-08-0497

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 94(02): 373-379
DOI: 10.1160/TH04-08-0497

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Quantification of thrombin activatable fibrinolysis inhibitor (TAFI) gene polymorphism effects on plasma levels of TAFI measured with assays insensitive to isoform-dependent artefact

Authors

Corinne Frère

¹INSERM UMR 626, Faculté de Médecine, Marseille, France
Pierre Emmanuel Morange

¹INSERM UMR 626, Faculté de Médecine, Marseille, France

²INSERM U 525, Faculté de Médecine, Hôpital Pitié-Salpêtrière, Paris, France
Noémie Saut

¹INSERM UMR 626, Faculté de Médecine, Marseille, France
David Alexandre Tregouet

²INSERM U 525, Faculté de Médecine, Hôpital Pitié-Salpêtrière, Paris, France
Mariana Grosley

³Serbio (Diagnostica Stago), Gennevilliers, France
Jérôme Beltran

³Serbio (Diagnostica Stago), Gennevilliers, France
Irène Juhan-Vague

¹INSERM UMR 626, Faculté de Médecine, Marseille, France
Marie-Christine Alessi

¹INSERM UMR 626, Faculté de Médecine, Marseille, France

Abstract

Summary

Reports have reappraised the genotype-dependent variation of Thrombin Activatable Fibrinolysis Inhibitor (TAFI), demonstrating that, in some enzyme-linked immunosorbent assays (ELISA), decreased antibody reactivity towards the TAFI 325 Ile isoform led to erroneous TAFI levels. Assays free of this artefact are required to evaluate the contribution of theTAFI gene polymorphisms toTAFI level variability.TAFI levels were measured in 209 individuals with both immunological and functional assays. Each assay was characterized, in particular for its reactivity towards the 325 Thr and Ile isoforms. Two ELISAs were found to have a lower reactivity towards the Ile isoform, leading to an overesti-mate of the magnitude of variation between two different genotypes. In contrast, one ELISA, as well as functional assays, was found to be free of genotype-dependent artefact constituting a reliable method to detect true quantitative variations of TAFI levels. Using these reliable methods, univariate and haplotype analyses revealed that TAFI gene polymorphisms explain 25% of TAFI level variability. This effect seems to be the consequence of the joint independent action of two polymorphisms, one in the 5’ (G-1102T) and the other in the 3’ region (T+1583A) of the TAFI gene.

Keywords

TAFI - monoclonal antibody - ELISA - genotype - polymorphism

Full Text

References

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