A CHI3L1 Gene Polymorphism is Associated with Serum Levels of YKL-40, a Novel Sarcoidosis Marker

Background: YKL-40, a chitinase-like cartilage glycoprotein, has recently shown its potential as a marker for sarcoidosis.

Methods: This study aimed to assess whether YKL-40 at presentation may predict the course of sarcoidosis over a 4-year follow-up period and to investigate whether polymorphisms in the chitinase 3-like 1 (CHI3L1) gene might influence serum YKL-40 levels in sarcoidosis patients (n=63) and controls (n=333).

Results: Patients had significantly higher (mean, 95% CI) serum YKL-40 levels (181.3 ng/ml, 50.7-648.1) compared to controls (36.6 ng/ml, p<0.0001. Serum YKL-40 was elevated in 79% of the patients and was inversely correlated with DLco at presentation (r(2)=-0.27, p=0.03), but not after 2-4 years of follow-up (r(2)=-0.16, p=0.27). Serum YKL-40 levels in controls were dependent on the CHI3L1 -329 G/A polymorphism (mean, 95% CI): GG (n=213) 48.3 ng/ml, 41.7-56.0; GA (n=101) 31.2 ng/ml, 26.6-36.3; AA (n=17) 17.8 ng/ml, 13.6-23.4, p<0.0001. In patients, this effect was not observed.

Conclusions: YKL-40 may be used as a sarcoidosis disease marker, but it is unsuitable as a marker to predict the course of the disease. The CHI3L1 -329 G/A polymorphism contributes to inter-individual variations of YKL-40 levels, but does not influence sarcoidosis disease susceptibility or severity.