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rs2431697 of miR-146a Regulates NETosis Determining the Thickness of the Carotid Intima-media in Patients with Rheumatoid Arthritis

1Deparment of Hematology and Medical Oncology, Morales Meseguer University Hospital, Centro Regional de Hemodonación, Universidad de Murcia, IMIB, Murcia, Spain, 2Rheumatology Service, Reina Sofia Hospital/Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/University of Cordoba, Córdoba, Spain, 3Deparment of Rheumatology, Morales Meseguer University Hospital, Murcia, Spain, 4Deparment of Internal Medicine, Morales Meseguer University Hospital, Murcia, Spain, 5Deparment of Radiology, Morales Meseguer University Hospital, Murcia, Spain

Abstract Number: LPB0040

Meeting: ISTH 2021 Congress

Theme: Vascular Biology » Non-coding RNAs

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease with cardiovascular complications in which immunothrombosis could take place. Our group has described, in other pathologies, that NET markers in plasma are associated with the rs2431697 of miR-146a whose carriers of the T-allele (<50% miR-146a levels) have increased risk of cardiovascular events.

Aims: Our objective is to explore whether rs2431697 is associated with NET markers and to study their relationship with the development of cardiovascular complications in patients with RA.

Methods: We collected clinical variables, plasma and DNA from RA patients (n=359) [mean age 55 (28-87), women 72%, 238 (66%) without biological drugs and 121 (34%) that received them during evolution] and samples from 50 controls. We genotyped rs2431697 using TaqMan probes and evaluated NETs in plasma by quantifying free-DNA (cfDNA) using SYTOXGreen and citrullinated-histone-H3 (citH3)/DNA complexes by ELISA. We evaluated the presence of atheroma plaques and quantified the thickness of the carotid intima (CIMT) using Doppler-ultrasonography.

Results: Frequencies of the rs2431697 genotypes did not show differences between patients and controls. We observed a higher proportion of carriers of T-allele in patients with biological drugs (p=0.05); in this group, citH3/DNA complexes were significantly higher in TT cohort (Fig.1). Doppler-ultrasonography data showed that values of both citH3/DNA (Fig.2A) and cfDNA (Fig.2B) were significantly higher in patients with vascular damage (59 vs 40; p=0.006; 64 vs 40; p=0.01, respectively). Interestingly, the highest levels of citH3/DNA in the pathological CIMT group corresponded to carriers of the T-allele (Fig.2B)
citH3+DNA (O.D.) according to genotype in the cohort of patients with biological drugs

A: citH3+DNA (O.D.) according to the result of carotid doppler ultrasonography. B: cfDNA (ng/µL) according to the result of carotid doppler ultrasongraphy.

Conclusions: We find that miR-146a rs2431697-T genotype is associated with the biological drug requirement and with greater intimal thickness in carriers. This suggests that miR-146a levels could influence both the clinical course and the thrombotic comorbidities associated with the disease.

To cite this abstract in AMA style:

Reguilón Gallego L, del los Reyes-García AM, Águila S, Fernández-Pérez MP, García Barberá N, Zapata-Martínez L, Ruiz Lorente I, Ábalos-Aguilera MC, Saiz E, Pina MF, Herranz MT, Barceló A, Hervés I, Vicente V, López-Pedrera C, Martínez C, González-Conejero R. rs2431697 of miR-146a Regulates NETosis Determining the Thickness of the Carotid Intima-media in Patients with Rheumatoid Arthritis [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/rs2431697-of-mir-146a-regulates-netosis-determining-the-thickness-of-the-carotid-intima-media-in-patients-with-rheumatoid-arthritis/. Accessed May 19, 2022.

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