Abstract
To determine if individuals with metabolic disorders possess unique gene expression profiles, we compared transcript levels in peripheral blood from patients with coronary artery disease, type 2 diabetes and their precursor state, metabolic syndrome to those of control subjects and subjects with rheumatoid arthritis. The gene expression profile of each metabolic state was distinguishable from controls and correlated with other metabolic states more than with rheumatoid arthritis. Of note, subjects in the metabolic cohorts over-expressed gene sets that participate in the innate immune response. Genes involved in activation of the pro-inflammatory transcription factor, NF-κB, were over-expressed in coronary artery disease while genes differentially expressed in type 2 diabetes play key roles in T cell activation and signaling. RT-PCR validation confirmed microarray results. Furthermore, several genes differentially expressed in human metabolic disorders have been previously shown to participate in inflammatory responses in murine models of obesity and Type 2 diabetes. Taken together, these data demonstrate that peripheral blood from individuals with metabolic disorders display overlapping and non-overlapping patterns of gene expression indicative of unique, underlying immune processes.
