Unique set of genes linked to obesity-linked asthma in young people
Disclosures: Xu does not report any relevant financial information. Please see the study for relevant financial information from all other authors.
According to a study published in Pediatric allergy and immunology.
Zhongli Xu, an MD-PhD candidate at Tsinghua University in Beijing, China, and a visiting scholar at the University of Pittsburgh, and colleagues wrote that obesity-related asthma is increasingly recognized as a phenotype distinct asthma with more severe severity and reduced response to bronchodilators and inhaled corticosteroids.
“Gene expression in the nasal epithelium correlates strongly with that of the bronchial epithelium, and thus nasal airway epithelium may serve as a surrogate marker for transcriptomics in the lower airway,” Xu wrote. and colleagues, adding that most previous studies have focused on blood. biomarkers.
To identify differentially expressed genes (DEGs) and pathways associated with obesity-related asthma, researchers conducted a transcriptome-wide association study (TWAS) in the nasal airway epithelium in young people at high risk of overweight or obesity and asthma.
The analysis included data from 235 Puerto Rican adolescents ages 9 to 20 from the Epigenetic Variation and Childhood Asthma Study and 66 children ages 6 to 16 from Pittsburgh in the Vitamin D Kids Asthma Study. Both studies included cohorts of overweight or obese with asthma (OOA) and normal weight with asthma (NWA) children.
The results of the transcriptome-wide meta-analysis revealed 29 DEG among young people with OOA, including CXCL11, CXCL10, CXCL9, CCL8, ISG15, £5, GBP1, SOCS1, GZMB, IFI35 and ISG20. None of these were significantly correlated with overweight or obesity in non-asthmatic children.
Moreover, only five of the 29 DEG – CXCL11, CCL8, LILRB1, SOCS1 and GZMB — appeared to be associated with overweight or obesity in young people without asthma.
Data from a functional enrichment analysis showed that the top 10 gene ontology biological processes overrepresented for the 29 DEGs associated with OOA included interferon-gamma production and the interferon signaling pathway of type I, T-cell and neutrophil chemotaxis and chemokine-mediated signaling pathways. Overall, most up-regulated pathways in OOA were those related to ciliary structure or function, while down-regulated pathways in OOA were those related to ciliary signaling. interferon, innate immune responses and adaptive immune response pathways.
Gene network analysis results revealed £5 as a “hub” gene unique to OOA; ISG15, SPATS2L and IFI25 as hub genes unique to NWA; and SOC21 as a central gene shared by OOA and NWA. The researchers also identified some co-expression patterns, such as the significantly higher co-expression of CXCL9 and VSXCL10 in OOA compared to NWA.
“We assume that increasing regulation CXCL9, CXCL10 and CXCL11 adipose tissue could induce a systemic response to low-grade interferon; this, combined with asthma-related interferon-mediated responses, could cause inhibited expression of CXCL9, CXCL10 and CXCL11 in the airways of OOA – which in turn may contribute to an impaired response to respiratory viral infections in patients with OOA,” the researchers wrote, adding that these findings warrant further study for the development of biomarkers or therapies.