Association between thrombin activatable fibrinolysis inhibitor genotype and levels in plasma: comparison of different assays

Abstract

Thrombin activatable fibrinolysis inhibitor (TAFI) antigen levels exhibit a large interindividual variability in which genetic control seems to play a major role. However, recent reports have questioned the association between TAFI concentration and genotype, suggesting that variable antibody reactivity towards TAFI isoforms, particularly the Thr325Ile polymorphism (1040C/T), may lead to artefacts in TAFI antigen levels. In order to compare assay outcome we determined plasma TAFI levels in 92 healthy individuals, using an enzyme-linked immunosorbent assay (ELISA) (commercial antibodies), an electroimmunoassay (in-house antibodies) and a commercial chromogenic assay (Actichrome(R) TAFI). Each individual was genotyped for the -438A/G and 1040C/T polymorphisms in the TAR gene. TAFI levels were significantly associated with genotype in both antigen and chromogenic assays. All assays displayed significant correlations with each other. Linear regression and Bland-Altman agreement analysis in the genotype subgroups showed that neither the genotype nor the concentration affected the relationship between the Actichrome(R) TAFI and the electroimmunoassay. In contrast, the ELISA/Actichrome(R) TAFI and the ELISA/electroimmunoassay relationships were concentration- and genotype-dependent. Our results demonstrate that artefacts may arise when measuring TAR antigen levels by ELISA. Nevertheless, the electroimmunoassay and the Actichrome(R) TAR assay support a genotype-related variation of TAFI concentration.