Pharmacogenetics of Asthma

Pharmacogenetics uses genetic information to help adjusting treatment for individual patients. It improves efficacy of therapy and enables avoiding side effects basing on genetic knowledge. Different asthmatic patients with similar disease severity, who are treated with the same medication, may respond to the therapy differently. After excluding non-genetic causes of such variability (like patient’s compliance, environmental and psychological factors), the most possible reason for the variability appears to be a different genetic structure. Changes in gene structure resulting in inter-individual dissimilarities, occur mostly as single nucleotide polymorphism (SNP). Different strategies play a role in searching and identifying SNPs, that influence pathogenesis of asthma and its response to treatment, (Kazani et al., 2010). One of the strategies involved is candidate gene studying, that focuses on finding genes responsible for therapy effectiveness as well as asthma development and its clinical severity (Moffatt & Cookson, 1997). Pharmacogenetics of asthma concentrates on genes coding: drug binding receptors, enzymes (important both in drug metabolism and metabolic cycles, eg. arachidonic acid cascade), chemokines, cytokines or growth factors relevant to asthma pathogenesis and pathophysiology. Genes need to be studied for known SNPs and new variants as well. When an SNP is found a thorough check for possible correlation between this polymorphism and disease phenotype or treatment response is needed. An expanded strategy for searching candidate genes involves screening of genes encoding proteins (enzymes) active in metabolic cycles important for drug response or key disease pathologies. In asthmatic patients this last method is often used to examine the leukotriene pathway in order to elucidate different patient reactions to leukotriene modifiers. Other options are genome-wide association studies that analyze genetic markers across the entire genome that may be connected with the phenotype. The identification of such a marker generated investigation of surrounding genes for SNPs related to the phenotype (Kazani et al., 2010). This procedure needs numerous and phenotypically well characterised populations and enables examination of the most frequent SNPs. There are some fields of medicine where pharmacogenetics is already in clinical use but in asthma treatment further investigation is still needed. This chapter reviews recent knowledge of pharmacogenetics of drugs commonly used in asthma treatment. We focus on bronchodilators, iCS (inhaled corticosteroids) and leukotriene modifiers.