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SAT0073 MIR-186-5P targeting IL-33 gene as biomarker to predict subclinical atherosclerosis in patients with early rheumatoid arthritis
  1. TH Cheng1,
  2. Q Shang1,
  3. WY Mak1,
  4. M Li1,
  5. KY Kwok2,
  6. ICW Yim3,
  7. EKM Li1,
  8. PCH Wong4,
  9. VWN Lao5,
  10. HT Pang5,
  11. LS Tam1
  1. 1Department of Medicine and Therapeutics, the Chinese University of Hong Kong
  2. 2Department of Medicine, Queen Elizabeth Hospital
  3. 3Department of Medicine, Tseung Kwan O Hospital
  4. 4Department of Medicine and Therapeutics, Prince of Wales Hospital
  5. 5Department of Medicine and Geriatrics, Kwong Wah Hosptial, Hong Kong, Hong Kong

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

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