{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:25:12Z","timestamp":1760239512879,"version":"build-2065373602"},"reference-count":151,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T00:00:00Z","timestamp":1605225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["SAF2015-70823-R, MINECO\/FEDER, UE"],"award-info":[{"award-number":["SAF2015-70823-R, MINECO\/FEDER, UE"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Brugada syndrome (BrS) is an inherited electrical heart disease associated with a high risk of sudden cardiac death (SCD). The genetic characterization of BrS has always been challenging. Although several cardiac ion channel genes have been associated with BrS, SCN5A is the only gene that presents definitive evidence for causality to be used for clinical diagnosis of BrS. However, more than 65% of diagnosed cases cannot be explained by variants in SCN5A or other genes. Therefore, in an important number of BrS cases, the underlying mechanisms are still elusive. Common variants, mostly located in non-coding regions, have emerged as potential modulators of the disease by affecting different regulatory mechanisms, including transcription factors (TFs), three-dimensional organization of the genome, or non-coding RNAs (ncRNAs). These common variants have been hypothesized to modulate the interindividual susceptibility of the disease, which could explain incomplete penetrance of BrS observed within families. Altogether, the study of both common and rare variants in parallel is becoming increasingly important to better understand the genetic basis underlying BrS. In this review, we aim to describe the challenges of studying non-coding variants associated with disease, re-examine the studies that have linked non-coding variants with BrS, and provide further evidence for the relevance of regulatory elements in understanding this cardiac disorder.<\/jats:p>","DOI":"10.3390\/ijms21228556","type":"journal-article","created":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T08:44:02Z","timestamp":1605257042000},"page":"8556","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Role of Non-Coding Variants in Brugada Syndrome"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1173-9794","authenticated-orcid":false,"given":"Adrian","family":"P\u00e9rez-Agust\u00edn","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, School of Medicine, University of Girona, 17003 Girona, Spain"},{"name":"Biomedical Research Institute of Girona, 17190 Salt, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7199-512X","authenticated-orcid":false,"given":"Mel\u00b7lina","family":"Pinsach-Abuin","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute of Girona, 17190 Salt, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0772-6982","authenticated-orcid":false,"given":"Sara","family":"Pagans","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, School of Medicine, University of Girona, 17003 Girona, Spain"},{"name":"Biomedical Research Institute of Girona, 17190 Salt, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1016\/0735-1097(92)90253-J","article-title":"Right bundle branch block, persistent ST segment elevation and sudden cardiac death: A distinct clinical and electrocardiographic syndrome. 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