Chitotriosidase gene polymorphisms and mutations limit the determination of chitotriosidase expression in sarcoidosis.

Serum chitotriosidase (CTO) activity was proposed as a biomarker in sarcoidosis being potentially useful in diagnostics. Nevertheless, a common duplication polymorphism (c.1049_1072dup24, Dup24) of the CTO gene influences CTO activity and thereby compromises its use in sarcoidosis. Here we aimed to substitute CTO activity with CTO concentration to prevent the confounding effect of Dup24. CTO activity, concentration and genetic backgrounds were determined in 80 histopathology proven sarcoidosis patients and 133 healthy individuals. CTO activities were lower in healthy individuals and sarcoidosis patients heterozygous for Dup24 mutation (472 ± 367 mU/L, n = 49; 2300 ± 2105 mU/L, n = 29) than in homozygous wild types (838 ± 856 mU/L, n = 81; 5125 ± 4802 mU/L, n = 48; p < 0.001, respectively). Sera of Dup24 homozygous individuals had no CTO activity. CTO concentrations were also lower in healthy individuals and sarcoidosis patients heterozygous for Dup24 mutation (7.2 ± 1.9 µg/L, n = 11; 63.16 ± 56.5 µg/L, n = 29) than in homozygous wild types (18.9 ± 13.0 µg/L, n = 36; 157.1 ± 132.4 µg/L, n = 47, p < 0.001, respectively) suggestive for an interaction between Dup24 mutation and CTO concentration determinations. We also identified a healthy Hungarian male subject without CTO activity carrying a rare mutation (c.(965_993)del), which mutation has been considered unique for Cypriot population to date. Taken together, CTO concentration determination does not add to the CTO activity measurement when CTO is used as a biomarker in sarcoidosis. Therefore, genotyping of CTO gene should be involved in the interpretation of laboratory findings.