Cardiac phenotype in familial partial lipodystrophy

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dc.contributor.authorEldin A.J.
dc.contributor.authorAkinci B.
dc.contributor.authorda Rocha A.M.
dc.contributor.authorMeral R.
dc.contributor.authorSimsir I.Y.
dc.contributor.authorAdiyaman S.C.
dc.contributor.authorOzpelit E.
dc.contributor.authorBhave N.
dc.contributor.authorGen R.
dc.contributor.authorYurekli B.
dc.contributor.authorOzdemir Kutbay N.
dc.contributor.authorSiklar Z.
dc.contributor.authorNeidert A.H.
dc.contributor.authorHench R.
dc.contributor.authorTayeh M.K.
dc.contributor.authorInnis J.W.
dc.contributor.authorJalife J.
dc.contributor.authorOral H.
dc.contributor.authorOral E.A.
dc.date.accessioned2024-07-22T08:06:01Z
dc.date.available2024-07-22T08:06:01Z
dc.date.issued2021
dc.description.abstractObjectives: LMNA variants have been previously associated with cardiac abnormalities independent of lipodystrophy. We aimed to assess cardiac impact of familial partial lipodystrophy (FPLD) to understand the role of laminopathy in cardiac manifestations. Study design: Retrospective cohort study. Methods: Clinical data from 122 patients (age range: 13–77, 101 females) with FPLD were analysed. Mature human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with an LMNA variant were studied as proof-of-concept for future studies. Results: Subjects with LMNA variants had a higher prevalence of overall cardiac events than others. The likelihood of having an arrhythmia was significantly higher in patients with LMNA variants (OR: 3.77, 95% CI: 1.45–9.83). These patients were at higher risk for atrial fibrillation or flutter (OR: 5.78, 95% CI: 1.04–32.16). The time to the first arrhythmia was significantly shorter in the LMNA group, with a higher HR of 3.52 (95% CI: 1.34–9.27). Non-codon 482 LMNA variants were more likely to be associated with cardiac events (vs. 482 LMNA: OR: 4.74, 95% CI: 1.41–15.98 for arrhythmia; OR: 17.67, 95% CI: 2.45–127.68 for atrial fibrillation or flutter; OR: 5.71, 95% CI: 1.37–23.76 for conduction disease). LMNA mutant hiPSC-CMs showed a higher frequency of spontaneous activity and shorter action potential duration. Functional syncytia of hiPSC-CMs displayed several rhythm alterations such as early afterdepolarizations, spontaneous quiescence and spontaneous tachyarrhythmia, and significantly slower recovery in chronotropic changes induced by isoproterenol exposure. Conclusions: Our results highlight the need for vigilant cardiac monitoring in FPLD, especially in patients with LMNA variants who have an increased risk of developing cardiac arrhythmias. In addition, hiPSC-CMs can be studied to understand the basic mechanisms for the arrhythmias in patients with lipodystrophy to understand the impact of specific mutations. © 2021 John Wiley & Sons Ltd
dc.identifier.DOI-ID10.1111/cen.14426
dc.identifier.issn03000664
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/13348
dc.language.isoEnglish
dc.publisherJohn Wiley and Sons Inc
dc.rightsAll Open Access; Green Open Access
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAged
dc.subjectFemale
dc.subjectHumans
dc.subjectInduced Pluripotent Stem Cells
dc.subjectLamin Type A
dc.subjectLipodystrophy
dc.subjectLipodystrophy, Familial Partial
dc.subjectMiddle Aged
dc.subjectMutation
dc.subjectPhenotype
dc.subjectRetrospective Studies
dc.subjectYoung Adult
dc.subjectisoprenaline
dc.subjectlamin A
dc.subjectaction potential
dc.subjectaction potential duration
dc.subjectadolescent
dc.subjectadult
dc.subjectaged
dc.subjectArticle
dc.subjectatrial fibrillation
dc.subjectcardiac muscle cell
dc.subjectchronotropism
dc.subjectclinical study
dc.subjectcodon
dc.subjectcohort analysis
dc.subjectcontrolled study
dc.subjectfamilial partial lipodystrophy
dc.subjectfemale
dc.subjectfibroblast
dc.subjectgene sequence
dc.subjectgenotype
dc.subjectglycemic control
dc.subjectheart arrhythmia
dc.subjectheart atrium flutter
dc.subjectheart disease
dc.subjectheart electrophysiology
dc.subjectheart ventricle extrasystole
dc.subjecthuman
dc.subjecthuman cell
dc.subjecthuman tissue
dc.subjectinduced pluripotent stem cell
dc.subjectKaplan Meier method
dc.subjectlaminopathy
dc.subjectlmna gene
dc.subjectmajor clinical study
dc.subjectmale
dc.subjectpathophysiology
dc.subjectpercutaneous coronary intervention
dc.subjectphenotype
dc.subjectprevalence
dc.subjectpriority journal
dc.subjectproof of concept
dc.subjectretrospective study
dc.subjecttachycardia
dc.subjectwhole exome sequencing
dc.subjectgenetics
dc.subjectinduced pluripotent stem cell
dc.subjectlipodystrophy
dc.subjectmiddle aged
dc.subjectmutation
dc.subjectphenotype
dc.subjectyoung adult
dc.titleCardiac phenotype in familial partial lipodystrophy
dc.typeArticle

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