Background and objectives Accelerated atherosclerosis, increased cardiovascular (CV) morbidity and mortality have been associated with rheumatoid arthritis (RA). In single SNP studies, CD40, HLADRB1, MTHFR, SMAD3 and possibly other alleles have been associated with cardiovascular disease (CVD) or vascular pathophysiology in RA. Endothelial dysfunction, carotid atherosclerosis and arterial stiffness that may predict the development of CVD are assessed by bracial artery flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and arterial pulse-wave velocity (PWV), respectively. In this study, we wished to determine expression profiles of multiple genes that may differentiate between physiological and pathological vascular function in RA.
Patients and methods Altogether 16 RA patients were recruited. FMD, ccIMT and PWV were assessed in all patients using standard B-mode ultrasound techniques. FMD < 6%, ccIMT > 0.6mm and PWV > 9 m/sec were considered abnormal. Peripheral blood mononuclear cell samples were obtained and used in microarray. The signature of those genes were determined by principal component analysis (PCA) and hierarchic clustering (GeneSpring software), which significantly differentiated patient subsets with normal vs. abnormal FMD, ccIMT and PWV.
Results Among RA patients, 11 had low (impaired) and 5 had normal FMD, 11 had high (increased) and 5 had normal ccIMT and 9 had high (increased) and 7 had normal PWV. Altogether 20 genes differentiated patients with low vs. normal FMD. Altogether 33 genes separated high vs. normal PWV. Finally, 240 genes differentiated increased vs. normal ccIMT.
Conclusions Using microarray, genetic signatures may differentiate RA patients with and without vascular pathology.