Quantification of thrombin activatable fibrinolysis inhibitor (TAFI) gene polymorphism effects on plasma levels of TAFI measured with assays insensitive to isoform-dependent artefact.
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 the TAFI gene polymorphisms to TAFI 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 overestimate 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.
Frère
Corinne
C
INSERM UMR 626, Faculté de Médecine, Marseille, France.
Morange
Pierre Emmanuel
PE
Saut
Noémie
N
Tregouet
David Alexandre
DA
Grosley
Mariana
M
Beltran
Jérôme
J
Juhan-Vague
Irène
I
Alessi
Marie-Christine
MC
D000483:Alleles; D016477:Artifacts; D025901:Carboxypeptidase B2 / Q000097:blood* / Q000235:genetics*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005821:Genetic Techniques; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D009203:Myocardial Infarction; D011110:Polymorphism, Genetic; D020033:Protein Isoforms; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity
D020033:Protein Isoforms; D025901:Carboxypeptidase B2