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Abstract
Background Patients with rheumatoid arthritis (RA) die prematurely compared with the general population, primarily because of cardiovascular diseases (CVD). Interleukin-33 (IL-33) is a member of the IL-1 cytokine family which was important in the pathogenesis of RA and development of CVD. Blood IL-33 protein was not detectable in most subjects, even in RA patients. Thus, the usability of IL-33 as a biomarker for CVD is limited. MicroRNAs (miRNAs) are small non-coding RNAs that function as post-transcriptional regulators of gene expression.
Objectives This study was to ascertain if dysregulated miRNAs targeting IL-33 gene in early RA (ERA) patients were associated with subclinical atherosclerosis in ERA patients.
Methods 76 ERA patients were recruited in this cross-sessional study. Potential miRNAs binding to 3'UTR of the IL-33 gene were predicted by miRanda (www.microRNA.org). 10 miRNAs with highest possibility targeting functional sites of IL-33 gene were quantified in cell free plasma samples using a 2Δ Ct method. Caenorhabditis elegans miR-39 (cel-miR-39) was used as spike-in control. The results were then log transferd. Carotid plaque (CP) was measured and identified at bilateral common carotid artery, bulb, and proximal internal carotid artery using a high-resolution B mode ultrasound. Receiver-operating characteristic curve (ROC) analysis was performed to determine the discriminating power of the miRNA for the presence of CP.
Results CPs were identified in 26/76 (34%) subjects (CP+ group). Subjects in the CP+ group were older [58±10 vs 48±11 years old, p=0.001], predominantly male [48 (42.3%) vs 43 (14.0%), p=0.006], with a higher C-reactive protein (CRP) level [24.9±25.0 vs 11.8±13.7 mg/dL, p=0.018] and higher cardiovascular risk [Framingham risk score (FRS): 12.8±11.6 vs 5.7±6.8, p=0.008] (Table 1). All miRNAs were detected in >80% of subjects in both group. Plasma level of miR-186–5p in the CP+ group was significantly higher than that in the CP- group [log miRNA: 3.28±3.21 vs 2.58±1.13 p=0.008]. It was still significant after adjusting age, sex, plasma CRP and FRS (p=0.030) (Table 1). Using multivariate logistic regression, miRNA-186–5p was an independent predictor of the presence of carotid plaque (OR: 1.919, 95% CI=1.096–3.361, p=0.023) after adjustment of FRS and CRP level. [Area under the ROC (AUC) 0.66, 95% CI: 0.60–0.80 p=0.024].
Conclusions miR-186–5p was an independent predictor for presence of subclinical atherosclerosis and may serve as a novel biomarker for risk stratification in ERA patients with mild to moderate cardiovascular risk.
Disclosure of Interest None declared