Meta-Analysis of Polymyositis and Dermatomyositis Microarray Data Reveals Novel Genetic Biomarkers.

Jaeseung Song,Hee Jung Park,Juyeon Hong,Jong Wha J Joo,Junghyun Jung,Daeun Kim,Go Woon Kim,Sejin Park,Wonhee Jang

doi:10.3390/genes10110864

Abstract

Polymyositis (PM) and dermatomyositis (DM) are both classified as idiopathic inflammatory myopathies. They share a few common characteristics such as inflammation and muscle weakness. Previous studies have indicated that these diseases present aspects of an auto-immune disorder; however, their exact pathogenesis is still unclear. In this study, three gene expression datasets (PM: 7, DM: 50, Control: 13) available in public databases were used to conduct meta-analysis. We then conducted expression quantitative trait loci analysis to detect the variant sites that may contribute to the pathogenesis of PM and DM. Six-hundred differentially expressed genes were identified in the meta-analysis (false discovery rate (FDR) < 0.01), among which 317 genes were up-regulated and 283 were down-regulated in the disease group compared with those in the healthy control group. The up-regulated genes were significantly enriched in interferon-signaling pathways in protein secretion, and/or in unfolded-protein response. We detected 10 single nucleotide polymorphisms (SNPs) which could potentially play key roles in driving the PM and DM. Along with previously reported genes, we identified 4 novel genes and 10 SNP-variant regions which could be used as candidates for potential drug targets or biomarkers for PM and DM.

Highlights

Idiopathic inflammatory myositis (IIM) is an extremely rare inflammatory myopathy, whose incidence was reported to be 7.98/million/year in literature based on meta-analysis using the data between 1966 and 2013 [1]
A total of three microarray datasets including those of PM/DM and healthy control samples were collected from EBI-ArrayExpress (Table 1)
Comparing the differentially expressed genes (DEGs) obtained from single studies and our merged study revealed that the meta-analysis could detect robust expression signatures which could not be detected in the single studies (Figure 1a,b)

Summary

Introduction

Idiopathic inflammatory myositis (IIM) is an extremely rare inflammatory myopathy, whose incidence was reported to be 7.98/million/year in literature based on meta-analysis using the data between 1966 and 2013 [1]. Polymyositis (PM) and dermatomyositis (DM) are the two most common types of IIM in developed countries, presenting muscle weakness and inflammation [2,3]. PM and DM are usually categorized together since the disease progression and muscle lesions are the same, irrespective of whether skin lesions are presented [4]. Serological features and clinical manifestations such as myositis-specific auto-antibodies were reported for both PM and DM in clinical studies [5,6]. The two diseases exhibit features of an auto-immune disorder; their exact pathogenesis has not been clearly demonstrated yet.

Methods

Results

Conclusion