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Childhood obesity progresses to metabolic disturbances via low-grade inflammation. Identifying novel molecules that reflect the activity of the immune responses is critical in understanding its underlying pathogenesis. Our exploratory study aimed to evaluate the change of chitotriosidase (CHIT1) plasma activity according to Body Mass Index (BMI)-for-age z score in pediatric patients. The study evaluated 68 children consisting of 47.1% girls with a mean age of 12.47 ± 3.71 years and 52.9% boys with a mean age of 11.93 ± 3.18 years. The effect of the most frequent CHIT1 gene variants, the 24 base pair duplication (dup24) and G102S polymorphism, upon the association between circulating CHIT1 activity and the obesity level, was also investigated. A significantly higher logCHIT1 plasma activity was found in children with extreme obesity than in children with overweight (p = 0.048 for the uncorrected CHIT1 and 0.026 for the corrected CHIT1). The BMI-for-age z score significantly (p = 0.031) predicts increased CHIT1 activity in children with overweight, obesity, and extreme obesity after controlling for the two gene variants, age, gender, and time since weight gain. Dup24 and G102S polymorphism were significant independent predictors (p-values < 0.002) for the change of CHIT1 plasma activity. Circulating CHIT1 might be an accurate indicator of inflammation in children with obesity. Its role and the effect of the dup24 and G102S variants on the CHIT1 activity should be validated in a larger cohort. Full article