Variation in airway remodelling genes and their role on asthma severity in children and young adults

Background: Asthma affects approximately 300 million people worldwide ', 5.2 million of these people live in the UK2, 1.1 million of these are children" Asthma is one of the most common chronic diseases and is the fourth leading cause of morbidity worldwide, and there is no indication of a decline in prevalence. It is hypothesised that a range of gene- environmental interactions may influence the susceptibility, severity and medication response of asthma in children and young adults". Methods: To explore these issues, two studies have been established to create datasets that will describe the phenotypic and genotypic characteristics of children with asthma in the paediatric population across Sussex and Scotland. This thesis is the output of doctoral research using data from these studies (BREATHE and PAGES) that aims to explore the interactions between variants of six genes implicated in airway remodelling and relevant environmental factors and their influence on the severity of asthma in children and young adults. This thesis is divided by analysis of individual variants. The thesis included one variant of Chitinase 3-Like-1, two variants of Matrix metalloproteinase 9, two variants of Matrix metalloproteinase 12, one variant of Matrix metalloproteinase 9, one variant of Glutathione S-tronsferase mu-1, one variant of Glutathione S-transferase theta-1 and one variant of Glutathione S-transferase pi-1. A total of eight variants were investigated. Variants were analysed for effect on multiple proxy measures of asthma severity, including asthma exacerbations, asthma treatment steps, pulmonary function and quality of life. Variants were also analysed for their effect on allergy.EThOS - Electronic Theses Online ServiceGBUnited Kingdo