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Darier disease is associated with heart failure: a cross-sectional case-control and population based study
Dermatology and Venereology Division, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden.
Dermatology and Venereology Division, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden; Dermato-Venereology Clinic, Karolinska University Hospital, Stockholm, Sweden.
Dermatology and Venereology Division, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden; Dermato-Venereology Clinic, Karolinska University Hospital, Stockholm, Sweden.
Dermatology and Venereology Division, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden.
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2020 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 6886Article in journal (Refereed) Published
Abstract [en]

Human data supporting a role for endoplasmic reticulum (ER) stress and calcium dyshomeostasis in heart disease is scarce. Darier disease (DD) is a hereditary skin disease caused by mutations in the ATP2A2 gene encoding the sarcoendoplasmic-reticulum Ca2+ ATPase isoform 2 (SERCA2), which causes calcium dyshomeostasis and ER stress. We hypothesized that DD patients would have an increased risk for common heart disease. We performed a cross-sectional case-control clinical study on 25 DD patients and 25 matched controls; and a population-based cohort study on 935 subjects with DD and matched comparison subjects. Main outcomes and measures were N-terminal pro-brain natriuretic peptide, ECG and heart diagnosis (myocardial infarction, heart failure and arrythmia). DD subjects showed normal clinical heart phenotype including heart failure markers and ECG. The risk for heart failure was 1.59 (1,16-2,19) times elevated in DD subjects, while no major differences were found in myocardial infarcation or arrhythmias. Risk for heart failure when corrected for cardivascular risk factors or alcohol misuse was 1.53 (1.11-2.11) and 1.58 (1,15-2,18) respectively. Notably, heart failure occurred several years earlier in DD patients as compared to controls. We conclude that DD patients show a disease specific increased risk of heart failure which should be taken into account in patient management. The observation also strenghtens the clinical evidence on the important role of SERCA2 in heart failure pathophysiology.

Place, publisher, year, edition, pages
Nature Publishing Group, 2020. Vol. 10, no 1, article id 6886
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Cardiology and Cardiovascular Disease
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URN: urn:nbn:se:oru:diva-89096DOI: 10.1038/s41598-020-63832-9ISI: 000530727600001PubMedID: 32327688Scopus ID: 2-s2.0-85083844417OAI: oai:DiVA.org:oru-89096DiVA, id: diva2:1523837
Available from: 2021-01-29 Created: 2021-01-29 Last updated: 2025-02-10Bibliographically approved

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Larsson, HenrikMartin, Cederlöf

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