Grant: Catalyst Grant: Environments, Genes and Chronic Disease

Asthma is a chronic respiratory disease which afflicts patients of all ages, causes significant morbidity and mortality and generates substantial costs to our society. Although the exact causes remain largely undefined, we know that genetic and environmental factors are important in development and symptoms of asthma. After huge efforts deployed to identify asthma genes, including Genome-wide associations studies, it is clearly apparent that the focus must be on 1) the integration of the environment in the refining of analyses for studies where genetic, clinical and exposition data are available, and 2) the development of experimental models (cellular, animal and/or analytic taking into account environmental factors) to better understand the role of the associated genes in asthma pathophysiology. In this context and based on previous encouraging genetics, epigenetics and expression data, the present catalyst focus on IL1R1 and IL1R2 genes and take into account tobacco smoking as environmental factor. Indeed, tobacco smoking is recognised to deteriorate lung function and increase the severity in asthma. In addition, tobacco exposure is well documented to have a large collection of epigenetic targets including proinflammatory cytokines. Our project provides a unique and valuable opportunity to decipher the impact of the IL1R1 and IL1R2 genes in asthma considering smoking status as environmental factor. The results will help to design future functional studies on these genes to ultimately develop new therapies.