Polimorfizmi gena povezanih s odgovorom na terapiju djece s astmom

Astma je najčešća kronična bolest u djece s trendom porasta prevalencije u budućnosti koju karakterizira izrazita heterogenost s obzirom na moguću etiologiju, stupanj upale i oštećenja bronha, poremećaj funkcije pluća i tijek bolesti. Astma se danas više ne smatra jedinstvenom bolešću nego sindromom s više različitih fenotipova definiranih novokoncipiranim imunopatoziološkim mehanizmima u kojem genska predispozicija igra važnu ulogu. Svrha ovog istraživanja je identificirati genske varijante povezane s učinkovitošću uobičajene terapije u astmi (inhalacijski kortikosteroidi, -agonisti i antagonisti leukotrienskih receptora) i specifične obrasce u odgovora na terapiju u astmi u djece (N= 365) te dati bolji uvid u patogenezu pojedinih podtipova bolesti. Rezultati ovog istraživanja pokazuju kako su određeni polimorfizmi u genima GLCCI1, TBX21, CRHR1, ADRB2 i MMP9 povezani s varijabilnim terapijskim ishodima te kako postoje diskretni obrasci terapijskih ishoda (pozitivni/ lošiji) povezani sa specifičnim fenotipskim karakteristikama poput razine i tipa upale, komorbiditeta i nekih genskih varijanti u djece s astmom.Asthma is the most common chronic condition in children. It is characterized by high levels of heterogeneity in disease etiology, inflammation, bronchial and lung function impairment and natural course of the disease. Asthma is no longer considered a single disease but rather an „umbrella“ term encompassing several different phenotypes defined by newly conceived pathophysiologic mechanisms and genetic predisposition. The purpose of this research is to identify genetic variants associated with treatment success in asthma (inhaled corticosteroids, -agonists, leukotriene receptor antagonists) and specific treatment response patterns in children, providing better insight into the pathogenesis of specific disease subtypes. The results of this study indicate that certain polymorphisms in the GLCCI1, TBX21, CRHR1, ADRB2 and MMP9 genes are associated with variable treatment outcomes in asthmatic children and that there may be discrete treatment outcome patterns (good/poor) associated with specific phenotype characteristics such as inflammation level and type, comorbidity and certain genetic traits