MMP9 gene polymorphisms as modulators of treatment response in asthma

Principal Investigator: Aleksandra Nikolic, PhD

Asthma is one of the most common chronic diseases of childhood, affecting millions of children (1 in 10), with increasing prevalence in most countries. This chronic airway disorder places severe limits on daily life and can be fatal, representing a serious global health problem and substantial socio-economic burden. According to the most recent guidelines issued by the Global Initiative for Asthma and National Heart, Lung and Blood Institute,efficient therapies for asthma are available, but the key to their successful implementation is the development of appropriate molecular tools to measure responsiveness to treatment in order to optimize therapy and achieve asthma control in each individual. Matrix metalloproteinase 9 (MMP9) is thought to be the major MMP in the airway of the asthmatics, affecting both airway remodeling and inflammation, with a suggested important role in asthma treatment also. Regulation of MMP9 gene expression is understudied. Several polymorphisms have been identified in 5’ untranslated region (5’-UTR) of the MMP9 gene that lead to an increased protein expression and/or higher risk for development of childhoodasthma, but were not investigated in light of the response to therapy. Polymorphisms in MMP9 gene 3’-UTR have not been studied in asthma, but may play a role in disease pathophysiology and response to therapy. This study will strive to elucidate the role of MMP9 gene regulationin response to the treatment of asthma. This will be achieved through clinical evaluation of treatment response in asthmatic children in correlation with the presence of polymorphisms in MMP9 gene regulatory regions. The main outcome of the study will be observed difference in response to treatment of asthma between carriers and non-carriers of certain polymorphisms, which could contribute to personalization of asthma treatment, and hence better control of the disease.