Evaluation of the Ankylosing Spondylitis Transcriptome for Oxidative Phosphorylation Pathway: The Shared Pathway with  Neurodegenerative Diseases

Arezou Lari; Hamid Gholami Pourbadie; Ali  Sharifi-Zarchi; Saeed Aslani; Leila  Nejatbakhsh Samimi; Ahmadreza Jamshidi; Mahdi Mahmoudi

doi:10.18502/ijaai.v20i5.7406

Arezou Lari Systems Biomedicine Unit, Pasteur Institute of Iran, Tehran, Iran
Hamid Gholami Pourbadie Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran
Ali Sharifi-Zarchi Department of Computer Engineering, Sharif University of Technology, Tehran, Iran
Saeed Aslani Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Leila Nejatbakhsh Samimi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Ahmadreza Jamshidi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Mahdi Mahmoudi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v20i5.7406

Keywords: Ankylosing spondylitis; Dementia; Gene expression; Oxidative phosphorylation

Abstract

Ankylosing spondylitis (AS) is a systemic inflammatory disorder of joints and entheses. Recent studies have reported an increased prevalence of dementia in AS patients. However, data for exploring the association between dementia and AS remain uncertain.

In this study, enriched pathways and differentially expressed genes (DEGs) were identified in whole blood transcription data of AS patients obtained from the gene expression omnibus (GEO) database; using gene set enrichment analysis (GSEA) and differential expression analysis.

Four pathways, including oxidative phosphorylation, Alzheimer’s, Parkinson’s, and Huntington’s diseases were significantly enriched in AS patients compared to the controls. We identified 22 common genes among the pathways that showed an increasing trend in AS compared to the controls. Five of them including COX7B, NDUFB3, ATP5PF, UQCRB, and NDUFS4 were the most significant genes which were selected for gene expression analysis; using real-time PCR on RNA contents of peripheral blood mononuclear cells (PBMCs) of AS patients and controls (20 samples from each group). The gene expression analysis indicated considerable overexpression of COX7B (p<0.0001) and ATP5J (p=0.0001) genes in AS patients group in comparison to the control samples.

The role of oxidative phosphorylation has previously been established in dementia pathogenesis. Given that AS patients have also a remarkably higher prevalence of dementia than the their healthy counterparts, hence our results may propose that the common pathway of oxidative phosphorylation can be regarded as a possible shared contributing factor in the etiopathogenesis of AS and dementia.