Cytokine genes as potential biomarkers for muscle weakness in OPMD

TY - JOUR

T1 - Cytokine genes as potential biomarkers for muscle weakness in OPMD

AU - Riaz, Muhammad

AU - Raz, Yotam

AU - van der Slujis, Barbara

AU - Dickson, George

AU - van Engelen, Baziel

AU - Vissing, John

AU - Raz, Vered

N1 - © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

PY - 2016/10/1

Y1 - 2016/10/1

N2 - 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.

AB - 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.

KW - Animals

KW - Biomarkers

KW - Cytokines

KW - Gene Expression Regulation

KW - Heterozygote

KW - Humans

KW - Mice

KW - Muscular Dystrophy, Oculopharyngeal

KW - Pathology, Molecular

KW - Poly(A)-Binding Protein I

KW - Quadriceps Muscle

KW - Transcriptome

KW - Journal Article

U2 - 10.1093/hmg/ddw259

DO - 10.1093/hmg/ddw259

M3 - Journal article

C2 - 27506982

SN - 0964-6906

VL - 25

SP - 4282

EP - 4287

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 19

ER -