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COPD is accompanied by coordinated transcriptional perturbation in the quadriceps affecting the mitochondria and ECM

ABSTRACT: In this experiment we catalogue transcriptional changes accompanying COPD in the quadriceps. We measure global gene transcription in the quadriceps using Affymetrix HuGene 1.1 ST arrays in an unselected cohort of 79 stable COPD patients in secondary care and 16 healthy age-and gender-matched controls. We identified 1,826 differentially expressed transcript clusters, comprising 6 modules of co-expressed genes, which differentially associate with clinical and immunological features of COPD.

ORGANISM(S): Homo sapiens

PROVIDER: GSE100281 | GEO | 2018/08/16

REPOSITORIES: GEO

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COPD is accompanied by co-ordinated transcriptional perturbation in the quadriceps affecting the mitochondria and extracellular matrix.

Project description:Skeletal muscle dysfunction is a frequent extra-pulmonary manifestation of Chronic Obstructive Pulmonary Disease (COPD) with implications for both quality of life and survival. The underlying biology nevertheless remains poorly understood. We measured global gene transcription in the quadriceps using Affymetrix HuGene1.1ST arrays in an unselected cohort of 79 stable COPD patients in secondary care and 16 healthy age- and gender-matched controls. We detected 1,826 transcripts showing COPD-related variation. Eighteen exhibited ?2fold changes (SLC22A3, FAM184B, CDKN1A, FST, LINC01405, MUSK, PANX1, ANKRD1, C12orf75, MYH1, POSTN, FRZB, TNC, ACTC1, LINC00310, MYH3, MYBPH and AREG). Thirty-one transcripts possessed previous reported evidence of involvement in COPD through genome-wide association, including FAM13A. Network analysis revealed a substructure comprising 6 modules of co-expressed genes. We identified modules with mitochondrial and extracellular matrix features, of which IDH2, a central component of the mitochondrial antioxidant pathway, and ABI3BP, a proposed switch between proliferation and differentiation, represent hubs respectively. COPD is accompanied by coordinated patterns of transcription in the quadriceps involving the mitochondria and extracellular matrix and including genes previously implicated in primary disease processes.

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