engleski

A polymorphism in the GLCCI1 gene is associated with response to common asthma treatment in children

Inhaled corticosteroids (ICS) are the most widely prescribed medications for controlling asthma. Levels of endogenous glucocorticoids are heritable and vary significantly, both at baseline and in response to environmental perturbation. The level of response to treatment with ICS is characterized by high intra-individual repeatability and high inter- individual variability with up to 50% of asthmatic patients having poor or even no response to treatment. Polymorphisms in GLCCI1, a gene important for the biological action of corticosteroids, has been associated with treatment response in asthmatics. To determine treatment outcomes in children with asthma in association with GLCCI1 (rs37973) genotype. We recruited 252 children with asthma and clinically assessed their health status and treatment outcome over the period of 12 months at 3 time points: at recruitment point, after 6 months and after 1 year (12 months). Genetic material was extracted from peripheral whole blood samples and then genotyped for the rs37973 polymorphism in the GLCCI1 gene. 210 children were treated with ICS continuously for at least 12 months. When treatment success was assessed by changes in asthma control according to GINA (Global Initiative for Asthma) guidelines (changes in lung function, symptom occurance, need for bronchodilatators) after 6 months of regular use of ICS, the frequency of AA genotype was significantly higher in good responders (p= 0, 0438) compared to the GG genotype. This genotype related response was even more evident when comparing patients with moderate and bad response to treatment with patients with good response: the frequency of AA genotype was also significantly higher in good responders versus moderate and bad (inadequate) responders (p= 0, 0331). The levels of response to treatment were defined as relative changes in asthma control (according to GINA) between clinical visits (assessments) at 3 time points. Our results showed that adequate levels of response to treatment with ICS in children with asthma (good treatment response), assessed as changes in asthma control parametres after 6 months of ICS use, are associated with a polymorphism in the GLCCI1 gene.

Inhaled corticosteroids ; children ; GLCCII

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