Prediction of human orthologs to the Drosophila’s COPD-associated genes

Background: The term Chronic Obstructive Pulmonary Disease (COPD) is used to describe chronic lung diseases that result in lung airflow limitations. WHO predicts that COPD will become the third leading cause of death worldwide by 2030. Aim: In this study, we aimed to identify the putative human functional equivalents of the fruit fly’s COPD-associated genes. Methods: We accessed the DIOPT-Diseases and Traits database (https://www.flyrnai.org/diopt-dist) for the prediction of the Drosophila melanogaster-Homo sapiens orthologs. To further test the results, we performed functional enrichment analysis (FEA) relative to disease of the retrieved human genes using the ToppFun tool of the ToppGene Suite (https://toppgene.cchmc.org/enrichment.jsp). Results: Ten human orthologs were identified (CHRNA3; cholinergic receptor nicotinic alpha 3 subunit, CSMD1; CUB and Sushi multiple domains 1, AP2A2; adaptor related protein complex 2 subunit alpha 2, ATF6; activating transcription factor 6, IREB2; iron responsive element binding protein 2, MCTP2; multiple C2 and transmembrane domain containing 2, FAM13A; family with sequence similarity 13 member A, CHID1; chitinase domain containing 1, CRACR2B; calcium release activated channel regulator 2B, HYKK; hydroxylysine kinase). The results of FEA confirmed that these particular genes are involved in COPD pathogenesis and are related to alpha-1 antitrypsin deficiency. Conclusions: GWAS genetic studies have identified loci associated with increased susceptibility to COPD. Our results identifying orthologs of Drosophila melanogaster and humans warrant further experimental evaluation as the predicted human genes are putative genetic determinants of COPD.