EAACI ISAF-RHINA Congress 2025
Exploring the impact of sex on asthma through transcriptomic analysis of airway epithelial cells
Elsa Garcia-Gonzalez, MSc1,2, Erick Castillo-Vargas, MSc1,2, Fabian Lorenzo-Diaz, PhD1, Maria Pino-Yanes, PhD1,2,3, Javier Perez-Garcia, PhD1,12
1 Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna (ULL), La Laguna, Tenerife, Spain.
2 Instituto de TecnologĂas BiomĂ©dicas (ITB), Universidad de La Laguna (ULL), La Laguna, Tenerife, Spain.
3 CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
Background: Asthma, a chronic inflammatory disease of the airways. Risk factors are diverse, but genetic predisposition is one of the most significant, disproportionately affecting women and men throughout different life stages.1 Risk factors are diverse, but genetic predisposition is one of the most significant. However, despite ample evidence highlighting the importance of sexual dimorphism in asthma, most omic studies conducted to date have not considered sex differences.2 Our aim was to identify differentially expressed genes by asthma status with differential effects in males and females, as well as their associated biological processes and metabolic pathways.
Methods: Publicly available RNA sequencing data from airway epithelium of asthmatic and non-asthmatic individuals (n085, GEO GSE85568) were used to perform a transcriptomic analysis of asthma stratified by sex.3 After quality control of the raw data, 54 samples were retained for downstream analysis. These were then aligned to the reference genome using STAR, quantified with RSEM, and subjected to differential expression analysis with DESeq2. Gene Ontology (GO) and KEGG pathway enrichment analyses were also performed. A comparison of the genes identified with the ones described in the GWAS Catalog and the ones from a previous gene expression study stratified by sex was carried out.
Results: The results revealed the presence of sex-specific differentially expressed genes (89 in females and 125 in males), with a greater involvement of interferon-mediated antiviral immune pathways in females, and metabolic and detoxification pathways in males. Furthermore, we replicated 13 genes described by a previous gene expression study stratified by sex and 6 genes overlapped with those described in previous genomic studies of asthma included in the GWAS Catalog.
Conclusion: The results of this study provide new evidence of sex-specific differences in the processes and pathways involved in asthma, which could have clinical implications for the design of more precise and personalized therapeutic strategies.
Funding: MICIU/AEI/10.13039/501100011033 (PID2020-116274RB-I00).