Abstract 10370: Circulating Mir-223-3p As A Novel Biomarker And Pathogenesis Of Brugada Syndrome

• Published in: Circulation (New York, N.Y.) Vol. 140; no. Suppl_1 Suppl 1; p. A10370
• Main Authors: Nakano, Yukiko, Onohara, Yuko, Motoda, Chikaaki, Tokuyama, Takehito, Hironobe, Naoya, Okubo, Yousaku, okamura, sho, Miyauchi, Shunsuke, Ikeuchi, Yoshihiro, Nishiyama, Orie, Ochi, Hidenori, Chayama, Kazuaki, Kihara, Yasuki
• Format: Journal Article
• Language: English
• Published: by the American College of Cardiology Foundation and the American Heart Association, Inc 19.11.2019
• ISSN: 0009-7322
• DOI: 10.1161/circ.140.suppl_1.10370

IntroductionBrugada syndrome (BrS) is able to be diagnosed by type1 BrS ECG. However, ECGs of BrS patients show day to day variations and diagnosis of BrS is sometimes challenging. Many susceptibility genes, other than main causative SCN5A gene, have been reported, but most patients with BrS do not have a genetic explanation. Circulating micro RNAs (miRNAs) have drawn great attention as potential biomarkers of various diseases.HypothesisWe hypothesized that the circulating miRNAs may play a role as diagnostic biomarkers for BrS.MethodsWe enrolled a total of 63 patients with BrS (44±14 years, 58 males and 5 females, 20 BrS patients had history of VF events) and 32 controls (31 males and 1 females, mean age 41±9 years) from Hiroshima University Hospital. Transverse sections of the septum of the right ventricle (RV) were obtained by biopsy from 21 BrS subjects and 20 patients to role out cardiomyopathy. Total RNA was extracted from individual plasma samples using the 3D-Gene RNA Extraction Reagent from a liquid sample kit. A total of 2,555 miRNA sequences were detected using the 3D-Gene miRNA Labeling kit and 3D-Gene Human miRNA Oligo Chip. To validate the microarray data, the total RNA samples extracted for microarray analysis were also used for quantitative revers transcription-PCR (qRT-PCR) analysis.ResultsThe 6 miRNA were down-regulated (miR-223-3p, miR-22-3p, miR-221-3p, miR-4485-5p, miR-550a-5p, miR-423-3p) and 6 miRNA were up-regulated (miR-873-3p, miR-23a-5p, miR-296-3p, miR-4718, miR-6132, miR-4515) more than 3 fold by 3D gene microarray analysis. Among them, the miR-223-3p was down-regulated not only in plasma RNA but also in RV tissue after validation of qRT-PCR.ConclusionThe circulating miR-223-3p becomes a novel biomarker of BrS. Down-regulation of the miR-223-3p may increase expression of KCND2/Kv4.2/Ito and relate to pathogenesis of BrS.