Cytokine genes as potential biomarkers for muscle weakness in OPMD

Research output: Contribution to journalJournal articleResearchpeer-review

  • Muhammad Riaz
  • Yotam Raz
  • Barbara van der Slujis
  • George Dickson
  • Baziel van Engelen
  • Vissing, John
  • Vered Raz

Molecular biomarkers emerge as an accurate diagnostic tool, but are scarce for myopathies. Lack of outcome measures sensitive to disease onset and symptom severity hamper evaluation of therapeutic developments. Cytokines are circulating immunogenic molecules, and their potential as biomarkers has been exploited in the last decade. Cytokines are released from many tissues, including skeletal muscles, but their application to monitor muscle pathology is sparse. We report that the cytokine functional group is altered in the transcriptome of oculopharyngeal muscular dystrophy (OPMD). OPMD is a dominant, late-onset myopathy, caused by an alanine-expansion mutation in the gene encoding for poly(A) binding protein nuclear 1 (expPABPN1). Here, we investigated the hypothesis that cytokines could mark OPMD disease state. We determined cytokines levels the vastus lateralis muscle from genetically confirmed expPABPN1 carriers at a symptomatic or a presymptomatic stage. We identified cytokine-related genes candidates from a transcriptome study in a mouse overexpressing exp PABPN1 Six cytokines were found to be consistently down-regulated in OPMD vastus lateralis muscles. Expression levels of these cytokines were highly correlated in controls, but this correlation pattern was disrupted in OPMD. The levels of these 6 cytokines were not altered in expPABPN1 carriers at a pre-symptomatic stage, suggesting that this group of cytokines is a potential biomarker for muscle weakness in OPMD. Correlation pattern of expression levels could be a novel measurer for disease state.

Original languageEnglish
JournalHuman Molecular Genetics
Volume25
Issue number19
Pages (from-to)4282-4287
Number of pages6
ISSN0964-6906
DOIs
Publication statusPublished - 1 Oct 2016

    Research areas

  • Animals, Biomarkers, Cytokines, Gene Expression Regulation, Heterozygote, Humans, Mice, Muscular Dystrophy, Oculopharyngeal, Pathology, Molecular, Poly(A)-Binding Protein I, Quadriceps Muscle, Transcriptome, Journal Article

ID: 180402796