Gene and miRNA expression profiles in PBMCs from patients with severe and mild emphysema and PiZZ alpha I-antitrypsin deficiency

Research output: Contribution to journalArticle

Abstract

Introduction: COPD has complex etiologies involving both genetic and environmental determinants. Among genetic determinants, the most recognized is a severe PiZZ (Glu342Lys) inherited alpha1-antitrypsin deficiency (AATD). Nonetheless, AATD patients present a heterogeneous clinical evolution, which has not been completely explained by sociodemographic or clinical factors. Here we performed the gene expression profiling of blood cells collected from mild and severe COPD patients with PiZZ AATD. Our aim was to identify differences in messenger RNA (mRNA) and microRNA (miRNA) expressions that may be associated with disease severity. Materials and methods: Peripheral blood mononuclear cells from 12 COPD patients with PiZZ AATD (6 with severe disease and 6 with mild disease) were used in this pilot, high-throughput microarray study. We compared the cellular expression levels of RNA and miRNA of the 2 groups, and performed functional and enrichment analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene-ontology (GO) terms. We also integrated the miRNA and the differentially expressed putative target mRNA. For data analyses, we used the R statistical language R Studio (version 3.2.5). Results: The severe and mild COPD-AATD groups were similar in terms of age, gender, exacerbations, comorbidities, and use of augmentation therapy. In severe COPD-AATD patients, we found 205 differentially expressed genes (DEGs) (114 upregulated and 91 downregulated) and 28 miRNA (20 upregulated and 8 downregulated) compared to patients with mild COPD-AATD disease. Of these, hsa-miR-335-5p was downregulated and 12 target genes were involved in cytokine signaling, MAPK/mk2, JNK signaling cascades, and angiogenesis were much more highly expressed in severe compared with mild patients. Conclusions: Despite the small sample size, we identified downregulated miRNA (hsa-miR-335) and the activation of pathways related to inflammation and angiogenesis on comparing patients with severe vs mild COPD-AATD. Nonetheless, our findings warrant further validation in large studies.

Details

Authors
  • Cristina Esquinas
  • Sabina Janciauskiene
  • Ricardo Gonzalo
  • Gemma Mas de Xaxars
  • Beata Olejnicka
  • Irene Belmonte
  • Miriam Barrecheguren
  • Esther Rodriguez
  • Alexa Nuñez
  • Francisco Rodriguez-Frias
  • Marc Miravitlles
Organisations
External organisations
  • Vall d'Hebron University Hospital
  • University of Barcelona
  • Hannover Medical School
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics

Keywords

  • Alpha1-antitrypsin deficiency, COPD, Gene expression, Integrative analysis, miRNAs
Original languageEnglish
Pages (from-to)3381-3390
Number of pages10
JournalInternational Journal of COPD
Volume12
Publication statusPublished - 2017 Nov 29
Publication categoryResearch
Peer-reviewedYes