Celedón Laboratory Publishes New Findings on Gene Expression Markers in Atopic Asthma

A new study published in the Journal of Allergy and Clinical Immunology from the Celedón Laboratory in the Division of Pediatric Pulmonary Medicine at UPMC Children's Hospital of Pittsburgh was aimed at discovering epigenetic and gene expression markers in the airway epithelium associated with atopic asthma in children.

Juan C. Celedón, MD, DrPH, ATSF, leads the lab efforts and is the chief of the Division of Pediatric Pulmonary Medicine at UPMC Children’s.

Dr. Celedón’s team collaborated with researchers from the Behavioral Sciences Research Institute at the University of Puerto Rico on this study.

By analyzing both cis- and trans-eQTM pairs—where DNA methylation affects gene expression nearby or at a distance, respectively—the research team sought to identify markers within the nasal epithelial samples from Puerto Rican youth with atopic asthma.

Cis- and trans-eQTM analysis are techniques to explore how DNA methylation affects gene activity or gene expression. Cis analysis focuses on methylation changes close to a gene to see how they directly alter the target gene's expression. Trans analysis looks at methylation changes located far away from the gene, potentially affecting the gene's activity indirectly. Both of these approaches explore how genes are regulated and can aid in identifying potential biomarkers of diseases or uncover possible new therapeutic targets by revealing connections between epigenetic modifications and gene function.

Study Highlights and Findings

The research team analyzed samples from 158 Puerto Rican children with atopic asthma and 100 control subjects, identifying a significant number of cis- and trans-eQTM pairs. The study found that trans-eQTM associations were enriched for genes regulated by transcription factors and microRNAs, which play important roles in controlling gene activity. These associations included genes previously implicated in asthma susceptibility and immune pathways. The study also sought to confirm its findings by comparing data from nasal epithelial samples from two other children's studies and in the white blood cells of the Puerto Rican participants.

The results of this analysis indicated that a substantial proportion of the eQTM pairs identified were consistent across different cohorts, adding to their potential relevance. Specifically, genes involved in the trans-eQTM analysis that were replicated in other cohorts included those with known connections to asthma.

The findings from this study suggest that analyzing both cis- and trans-eQTM can unveil mechanistic pathways and networks that may underlie childhood asthma. The discovery of trans-eQTM CpGs that potentially regulate gene expression through transcription factors and microRNA target genes provides new understandings of the molecular mechanisms of atopic asthma.

For future clinical practice, this research could aid in the development of new biomarkers for early detection or the progression of asthma, while also helping to inform more personalized treatment strategies for patients. Further research based on these findings could focus on exploring the therapeutic potential of targeting specific methylation sites to modulate gene expression with the end goals of either preventing asthma from occurring or treating existing disease.

Reference

Kim S, Xu Z, Forno E, Qin Y, Park HJ, Yue M, Yan Q, Manni ML, Acosta-Pérez E, Canino G, Chen W, Celedón JC. Cis- and Trans-eQTM Analysis Reveals Novel Epigenetic and Transcriptomic Immune Markers of Atopic Asthma in Airway Epithelium. J Allergy Clin Immunol. 2023 Oct; 152(4): 887-898.