Abstract
Asthma is a common and heterogeneous disease characterized by chronic airway inflammation. Currently, the two main types of asthma medicines are inhaled corticosteroids and long-acting β2-adrenoceptor agonists (LABAs). In addition, biological drugs provide another therapeutic option, especially for patients with severe asthma. However, these drugs were less effective in preventing severe asthma exacerbation, and other drug options are still limited. Herein, we extracted asthma-associated single nucleotide polymorphisms (SNPs) from the genome-wide association studies (GWAS) and phenome-wide association studies (PheWAS) catalog and prioritized candidate genes through five functional annotations. Genes enriched in more than two categories were defined as “biological asthma risk genes.” Then, DrugBank was used to match target genes with FDA-approved medications and identify candidate drugs for asthma. We discovered 139 biological asthma risk genes and identified 64 drugs targeting 22 of these genes. Seven of them were approved for asthma, including reslizumab, mepolizumab, theophylline, dyphylline, aminophylline, oxtriphylline, and enprofylline. We also found 17 drugs with clinical or preclinical evidence in treating asthma. In addition, eleven of the 40 candidate drugs were further identified as promising asthma therapy. Noteworthy, IL6R is considered a target for asthma drug repurposing based on its high target scores. Through in silico drug repurposing approach, we identified sarilumab and satralizumab as the most promising drug for asthma treatment.
Highlights
Asthma is a prevalent chronic respiratory disease that can adversely influence patients’quality of life of all ages and genders
Based on the characteristic of r2 > 0.8 used in Asian populations, we extended the number of single nucleotide polymorphisms (SNPs) by HaploReg v4.1 and obtained 1047 asthma risk genes (Table S2)
The scoring results were as follow: (1) genes include asthma risk missense variant (n = 66); (2) genes with Cis-eQTL effect (n = 72); (3) genes prioritized by KO mice (n = 84); (4) genes prioritized by Protein–protein interactions (PPIs) (n = 284); and (5) genes prioritized by a molecular pathway (n = 88)
Summary
Asthma is a prevalent chronic respiratory disease that can adversely influence patients’quality of life of all ages and genders. Asthma is a prevalent chronic respiratory disease that can adversely influence patients’. A heterogeneous disease, is classified into different clinical phenotypes such as allergic asthma, non-allergic asthma, adult-onset asthma, asthma with persistent airflow limitation, and asthma with obesity [3]. Biomedicines 2022, 10, 113 have asthma, with an estimated prevalence rate of 1–18%. In addition to the rising prevalence, morbidity and mortality rates have increased over the past few decades [1,4,5]. The increasing number of asthma patients is a burden to medical investments and represents increased care costs for families and communities [5]. Studies of gene–environmental interactions may help elucidate disease mechanisms and classify particular genes or exposures in the same pathway [8]
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