{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T19:03:30Z","timestamp":1782414210538,"version":"3.54.5"},"reference-count":22,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022654","name":"Hudfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022654","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003748","name":"Svenska S\u00e4llskapet f\u00f6r Medicinsk Forskning","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003748","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012331","name":"LEO Fondet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012331","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ALF medicin Stockholm"},{"DOI":"10.13039\/100008738","name":"Jeanssons Stiftelser","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011898","name":"Marcus och Amalia Wallenbergs minnesfond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011898","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010823","name":"Tore Nilsons Stiftelse f\u00f6r Medicinsk Forskning","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010823","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Hailey-Hailey disease (HHD) is a rare autosomal dominant skin disease caused by mutations in the <jats:italic>ATP2C1<\/jats:italic> gene, which encodes the secretory Ca<jats:sup>2+<\/jats:sup>\/Mn<jats:sup>2+<\/jats:sup>-ATPase (SPCA1) pump in the Golgi apparatus. Although <jats:italic>ATP2C1<\/jats:italic> is ubiquitously expressed in the body, possible extracutaneous manifestations of HHD are unknown. However, dysfunction of the Golgi apparatus not specifically coupled to <jats:italic>ATP2C1<\/jats:italic> has been associated with heart disease.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>To investigate the association between HHD and common heart disease in a Swedish, population-based cohort.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We conducted a population-based cohort study based on a linkage of Swedish nationwide registers to investigate the relationship between HHD and heart disease. We have been granted ethical approval from the Swedish Ethical Review Authority to conduct this study. The patients in this manuscript have given written informed consent to the publication of their case details. A total of 342 individuals with an ICD-10 diagnosis of HHD (Q82.8E) were identified and matched with randomly selected comparison individuals without HHD on a 1:100 ratio. Furthermore, in a separate clinical cohort we matched 23 HHD patients for age, sex, and BMI with control subjects to examine electrocardiogram parameters, electrolytes, and cardiovascular biomarkers.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>Compared with individuals without HHD, individuals with HHD had an excess risk of arrhythmia (RR 1.4, CI 1.0\u20132.0), whereas no increased risks of myocardial infarction (RR 1.1, CI 0.6\u20131.7) or heart failure (RR 1.0, CI 0.6\u20131.6; Table 1) were found. We found no difference in ECG parameters, cardiovascular biomarkers, and electrolytes in the clinical subset.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This study reveals that HHD is associated with an increased risk of arrhythmia and represents the first data of any extracutaneous comorbidity in HHD. Thus, HHD may be a systemic disease. Our findings also shed light on the importance of the Golgi apparatus\u2019 Ca<jats:sup>2+<\/jats:sup>\/Mn<jats:sup>2+<\/jats:sup> homeostasis in common heart disease.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0309482","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T18:09:05Z","timestamp":1725646145000},"page":"e0309482","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Increased risk of cardiac arrhythmia in Hailey-Hailey disease patients"],"prefix":"10.1371","volume":"19","author":[{"given":"William","family":"Jebril","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Curman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel 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