engleski

Gene polymorphisms associated with treatment outcome in asthmatic children

The goal: Treatment for asthma is designed in a “one size fits all” approach, frequently leading to over- or under-medication, which is why we wanted to identify genetic variants predisponing for the interindividual variability in the response to common asthma medications, and to evaluate treatment outcome in asthmatic children. Material and methods: Treatment outcomes were assessed in 365 children (aged 2-18 years) with atopic and non- atopic, intermitent to moderate persistent asthma, over the period of 2 years. Patients were followed 6 months apart, according to relative changes in lung function parameters (FEV1, MEF50), FENO levels, level of disease control and exacerbation rate. These were then associated with genotype and allele frequencies for polymorphisms in the GLCCI1 gene (rs37973), TBX21 gene (rs9910408), CRHR1 gene (rs242941 and rs1876828), ADRB2 gene (rs1042713) and MMP9 gene (rs17576) in patients, using different classes of treatment (ICS alone, LTRA alone and combination treatment - ICS+LABA/LTRA). Results: The subsequent analysis of genotypes revealed 4 different cluster. Clusters 1 and 3 had a more positive pattern of treatment outcomes and were characterized by more prominent atopic markers and a predominant allelic (A allele) effect for rs37973 in the GLCCI1 gene, previously associated with positive treatment outcomes in asthmatics. These patients also had a relatively later onset of disease (6+ yrs). Clusters 2 and 4 had poorer treatment success and were characterized by higher levels of airway and systemic inflammation, but varied in the type of inflammation (predominantly neutrophilic for cluster 4 and likely mixed-type for cluster 2), comorbidities (obesity for cluster 2) and platelet count (lowest for cluster 4). Conclusion: A better understanding of individual variations in response to treatment will help clinicians in optimising asthma treatment and enable each patient to have full quality of life with minimal or no impediment from their asthma.

Asthma ; children ; gene polymorphisms

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