The Pharmacogenomics of Asthma Beyond Its Endotypes

Background: While endotype-driven therapeutic strategies are increasingly successful for asthma, the issues of dissociated effect and drug efficacy at the target sites remain unresolved. This review is to provide a comprehensive overview of the pharmacogenomics of asthma along with its endotype subsets.

Methods: We undertook a search in NCBI All Databases by key words "pharmacogenomics AND allergen", "pharmacogenomics AND asthma AND rhinitis", etc. The remaining papers were reviewed without bias after the exclusion of redundant papers and non-English papers (except for Chinese papers). Papers regarding similar issues or items were then pooled together to support the corresponding viewpoints and subtitles, conclusions were thus drawn.

Result: Eighty of the retrieved 139 papers were included in the review. Immunopathogenesis of asthma found that the induction of asthma involves genetic variation, TLR gene-activated immune responses, cell-mediated inflammation, and other immunological changes. Human lung mast cell has a crucial effect on the symptoms of asthma. JAK-3 mediates cytokine signaling, while DNA methylation in the ADRB2 gene decreases asthma symptom severity. Pharmacotherapeutics of asthma has focused on fewer candidate genes, relating to glucocorticoid, leukotriene, and β2-adrenergic receptor pathways, and other pathways involving IgE, IL-5, IL-4, IL-13 and IL-17.

Conclusion: The genetic profiles of gene variants can predict individual disease susceptibility and risk for disease progression. Fewer genes, relating to glucocorticoid, leukotriene, histamine, and β2-adrenergic receptor pathways, have been concentrated. A personalized, tailored approach is necessary for health care delivery according to the individual variability in genes, environment and lifestyle of each individual.