Unique set of genes linked to obesity-related asthma in youth

Researchers identified 29 genes in the nasal airway epithelium of adolescents that correlated with obesity-related asthma, 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 research scholar at University of Pittsburgh, and colleagues wrote that obesity-related asthma is increasingly recognized as a distinct asthma phenotype with worse severity and reduced response to bronchodilators and inhaled corticosteroids.

“Gene expression in the nasal epithelium is highly correlated with that in bronchial epithelium, and thus the nasal airway epithelium can serve as a surrogate marker for transcriptomics in the lower airways,” Xu and colleagues wrote, adding that most prior studies have focused on blood biomarkers.

To identify differently expressed genes (DEGs) and pathways associated with obesity-related asthma, the researchers conducted a transcriptome-wide association study (TWAS) in nasal airway epithelium among young individuals who were at a high risk for both overweight or obesity and asthma.

The analysis included data from 235 Puerto Rican adolescents aged 9 to 20 years from the Epigenetic Variation and Childhood Asthma study and 66 children aged 6 to 16 years from Pittsburgh in the Vitamin D Kids Asthma study. Both studies included cohorts of children with overweight or obesity with asthma (OOA) and normal weight with asthma (NWA).

Results of the transcriptome-wide meta-analysis revealed 29 DEGs among the youth with OOA, including CXCL11, CXCL10, CXCL9, CCL8, ISG15, GBP5, GBP1, SOCS1, GZMB, IFI35 and ISG20. None of these correlated significantly with overweight or obesity in children without asthma.

Additionally, only five of the 29 DEGs — CXCL11, CCL8, LILRB1, SOCS1 and GZMB — appeared associated with overweight or obesity in youth without asthma.

Data from a functional enrichment analysis showed that the top 10 over-represented gene ontology biological processes for the 29 DEGs associated with OOA included interferon-gamma production and type-I interferon signaling pathway, T cell and neutrophil chemotaxis and chemokine-mediated signaling pathways. Overall, most of the upregulated pathways in OOA were those related to ciliary structure or function, whereas the downregulated pathways in OOA were those related to interferon signaling, innate immune responses and adaptive immune response pathways.

Results of a gene network analysis revealed GBP5 as a “hub” gene unique to OOA; ISG15, SPATS2L and IFI25 as hub genes unique to NWA; and SOC21 as a hub gene shared by both OOA and NWA. Researchers also identified some co-expression patterns, such as the markedly higher co-expression of CXCL9 and CXCL10 in OOA compared with NWA.

“We surmise that up-regulated CXCL9, CXCL10 and CXCL11 from adipose tissue could induce a low-grade systemic interferon response; this, combined with interferon-mediated responses related to asthma, could elicit inhibited expression of CXCL9, CXCL10 and CXCL11 in the airways of OOA — which could in turn contribute to an impaired response to respiratory viral infections in patients with OOA,” the researchers wrote, adding that these results warrant additional study for the development of biomarkers or therapies.