ARID5B Overexpression in Inflammatory Diseases
This diagnostic assay predicts disease pathophysiology of pro-inflammatory diseases such as diabetes and atherosclerosis by quantifying ARID5B gene expression and determining the methylation status of the gene. ARID5B expression in monocytes has strong co-relation to the development of atherosclerosis and other pro-inflammatory diseases, so monitoring ARID5B gene expression can assist clinicians when making early intervention treatment decisions.
Although traditional risk factors for atherosclerosis are established, there is substantial unexplained variation in the atherosclerosis phenotype. The risk factors for plaque vulnerability are largely unknown and, while genome-wide association studies have identified a number of susceptibility variants, they explain only a small percent of cardiovascular disease risk. Available therapies primarily target hyperlipidemia and prevention of thrombosis, which indicates manifestation of cardiovascular disease pathophysiology.
Scientists at Wake Forest Baptist Medical Center have identified transcriptome and methylome signatures associated with subclinical and clinical atherosclerosis, specifically the expression of a gene, ARID5B, which is positively associated with atherogenesis. ARID5B CpG methylation is inversely associated with both ARID5B expression and atherosclerosis, consistent with this CpG residing in an ARID5B enhancer region. ARID5B expression promotes atherosclerosis by dysregulating immunometabolism toward a chronic inflammatory phenotype.
A study was conducted on human samples collected from the MESA cohort (N=1208). Expression of ARID5B was positively associated with both measures of atherosclerosis; carotid plaque burden (carotid plaque score, range 0-12) and coronary artery calcification (CAC Agatston score), respectively. In vitro functional analysis of ARID5B gene expression was conducted in THP-1 monocytes.
• Yongmei Liu, MD, PhD, Department of Epidemiology and Prevention
• Jingzhong Ding, MD, PhD, Section of Gerontology and Geriatric
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Osama Zahid, PhD