Genetic polymorphisms associated with the response to asthma treatment in children

doctoral thesis

• Title (croatian): Polimorfizmi gena povezanih s odgovorom na terapiju djece s astmom
• Author: Ivana Banić
• Mentor: Mirjana Turkalj (mentor)
• Committee member: Kristian Vlahoviček (predsjednik povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2019-03-22, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 577 - Biochemistry. Molecular biology. Biophysics

Abstract

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.

Abstract (english)

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.

• Keywords: astma; terapija; genski polimorfizmi; djeca; uspješnost terapije; inhalacijski kortikosteroidi; fenotipovi u astmi
• Keywords (english): asthma; treatment; genetic polymorphisms; children; treatment success; inhaled corticosteroids; asthma phenotypes
• Language: croatian
• URN:NBN: urn:nbn:hr:217:586917
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2019-04-10 08:34:59