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Plakophilin-2 c.419C>T and risk of heart failure and arrhythmias in the general population

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Plakophilin-2 c.419C>T and risk of heart failure and arrhythmias in the general population. / Christensen, Alex Hørby; Kamstrup, Pia Rørbœk; Gandjbakhch, Estelle; Benn, Marianne; Jensen, Jan Skov; Bundgaard, Henning; Villard, Eric; Tybjærg-Hansen, Anne.

I: European Journal of Human Genetics, Bind 24, Nr. 5, 05.2016, s. 732-8.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Christensen, AH, Kamstrup, PR, Gandjbakhch, E, Benn, M, Jensen, JS, Bundgaard, H, Villard, E & Tybjærg-Hansen, A 2016, 'Plakophilin-2 c.419C>T and risk of heart failure and arrhythmias in the general population', European Journal of Human Genetics, bind 24, nr. 5, s. 732-8. https://doi.org/10.1038/ejhg.2015.171

APA

Christensen, A. H., Kamstrup, P. R., Gandjbakhch, E., Benn, M., Jensen, J. S., Bundgaard, H., ... Tybjærg-Hansen, A. (2016). Plakophilin-2 c.419C>T and risk of heart failure and arrhythmias in the general population. European Journal of Human Genetics, 24(5), 732-8. https://doi.org/10.1038/ejhg.2015.171

Vancouver

Christensen AH, Kamstrup PR, Gandjbakhch E, Benn M, Jensen JS, Bundgaard H o.a. Plakophilin-2 c.419C>T and risk of heart failure and arrhythmias in the general population. European Journal of Human Genetics. 2016 maj;24(5):732-8. https://doi.org/10.1038/ejhg.2015.171

Author

Christensen, Alex Hørby ; Kamstrup, Pia Rørbœk ; Gandjbakhch, Estelle ; Benn, Marianne ; Jensen, Jan Skov ; Bundgaard, Henning ; Villard, Eric ; Tybjærg-Hansen, Anne. / Plakophilin-2 c.419C>T and risk of heart failure and arrhythmias in the general population. I: European Journal of Human Genetics. 2016 ; Bind 24, Nr. 5. s. 732-8.

Bibtex

@article{63b615c701d44a28a50117c916b1a634,
title = "Plakophilin-2 c.419C>T and risk of heart failure and arrhythmias in the general population",
abstract = "A rare genetic variant in the desmosomal gene plakophilin-2 (PKP2) c.419C>T(p.(S140F)) has repeatedly been identified in patients with dilated cardiomyopathy (DCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC). Whether this is a disease-causing variant remains highly controversial. We tested this hypothesis using three approaches. Initially, in a prospective study of 10 407 individuals from the general population, including 2688 who developed heart failure or arrhythmias during >14 years of follow-up, PKP2 c.419C>T was identified in 98 individuals (0.94{\%}). PKP2 genotype was not associated with electrocardiographic or echocardiographic changes, or with plasma levels of probrain natriuretic peptide (all P≥0.05). In c.419C>T carriers versus non-carriers, multifactorially adjusted hazard ratios were 1.26 (95{\%} confidence interval: 0.77-2.07) for heart failure, 1.40 (0.90-2.17) for arrhythmias, 1.15 (0.78-1.71) for end points combined, and 1.33 (0.98-1.80) for all-cause mortality. The cumulative survival as a function of age and PKP2 genotype was similar among carriers and non-carriers (P=0.14). Second, comparing 517 patients referred for genetic testing with 1918 matched controls, odds ratios as a function of c.419C>T genotype were 2.11 (0.50-8.99) for ARVC, 0.72 (0.16-3.28) for hypertrophic cardiomyopathy (HCM)/DCM, and 1.28 (0.46-3.54) for end points combined. Third, in in vitro studies cellular localization of plakophilin-2, plakoglobin, connexin-43, or N-cadherin were similar in cells transfected with wild-type or mutant plakophilin-2. In conclusion, combining epidemiological data, with data on patients referred for genetic testing for ARVC or HCM/DCM, and data from in vitro studies, PKP2 c.419C>T did not associate with heart failure, arrhythmias, or premature death, with ARVC or HCM/DCM, or with effects in vitro, suggesting that this is not a disease-causing variant.",
keywords = "Journal Article",
author = "Christensen, {Alex H{\o}rby} and Kamstrup, {Pia R{\o}rbœk} and Estelle Gandjbakhch and Marianne Benn and Jensen, {Jan Skov} and Henning Bundgaard and Eric Villard and Anne Tybj{\ae}rg-Hansen",
year = "2016",
month = "5",
doi = "10.1038/ejhg.2015.171",
language = "English",
volume = "24",
pages = "732--8",
journal = "European Journal of Human Genetics",
issn = "1018-4813",
publisher = "nature publishing group",
number = "5",

}

RIS

TY - JOUR

T1 - Plakophilin-2 c.419C>T and risk of heart failure and arrhythmias in the general population

AU - Christensen, Alex Hørby

AU - Kamstrup, Pia Rørbœk

AU - Gandjbakhch, Estelle

AU - Benn, Marianne

AU - Jensen, Jan Skov

AU - Bundgaard, Henning

AU - Villard, Eric

AU - Tybjærg-Hansen, Anne

PY - 2016/5

Y1 - 2016/5

N2 - A rare genetic variant in the desmosomal gene plakophilin-2 (PKP2) c.419C>T(p.(S140F)) has repeatedly been identified in patients with dilated cardiomyopathy (DCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC). Whether this is a disease-causing variant remains highly controversial. We tested this hypothesis using three approaches. Initially, in a prospective study of 10 407 individuals from the general population, including 2688 who developed heart failure or arrhythmias during >14 years of follow-up, PKP2 c.419C>T was identified in 98 individuals (0.94%). PKP2 genotype was not associated with electrocardiographic or echocardiographic changes, or with plasma levels of probrain natriuretic peptide (all P≥0.05). In c.419C>T carriers versus non-carriers, multifactorially adjusted hazard ratios were 1.26 (95% confidence interval: 0.77-2.07) for heart failure, 1.40 (0.90-2.17) for arrhythmias, 1.15 (0.78-1.71) for end points combined, and 1.33 (0.98-1.80) for all-cause mortality. The cumulative survival as a function of age and PKP2 genotype was similar among carriers and non-carriers (P=0.14). Second, comparing 517 patients referred for genetic testing with 1918 matched controls, odds ratios as a function of c.419C>T genotype were 2.11 (0.50-8.99) for ARVC, 0.72 (0.16-3.28) for hypertrophic cardiomyopathy (HCM)/DCM, and 1.28 (0.46-3.54) for end points combined. Third, in in vitro studies cellular localization of plakophilin-2, plakoglobin, connexin-43, or N-cadherin were similar in cells transfected with wild-type or mutant plakophilin-2. In conclusion, combining epidemiological data, with data on patients referred for genetic testing for ARVC or HCM/DCM, and data from in vitro studies, PKP2 c.419C>T did not associate with heart failure, arrhythmias, or premature death, with ARVC or HCM/DCM, or with effects in vitro, suggesting that this is not a disease-causing variant.

AB - A rare genetic variant in the desmosomal gene plakophilin-2 (PKP2) c.419C>T(p.(S140F)) has repeatedly been identified in patients with dilated cardiomyopathy (DCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC). Whether this is a disease-causing variant remains highly controversial. We tested this hypothesis using three approaches. Initially, in a prospective study of 10 407 individuals from the general population, including 2688 who developed heart failure or arrhythmias during >14 years of follow-up, PKP2 c.419C>T was identified in 98 individuals (0.94%). PKP2 genotype was not associated with electrocardiographic or echocardiographic changes, or with plasma levels of probrain natriuretic peptide (all P≥0.05). In c.419C>T carriers versus non-carriers, multifactorially adjusted hazard ratios were 1.26 (95% confidence interval: 0.77-2.07) for heart failure, 1.40 (0.90-2.17) for arrhythmias, 1.15 (0.78-1.71) for end points combined, and 1.33 (0.98-1.80) for all-cause mortality. The cumulative survival as a function of age and PKP2 genotype was similar among carriers and non-carriers (P=0.14). Second, comparing 517 patients referred for genetic testing with 1918 matched controls, odds ratios as a function of c.419C>T genotype were 2.11 (0.50-8.99) for ARVC, 0.72 (0.16-3.28) for hypertrophic cardiomyopathy (HCM)/DCM, and 1.28 (0.46-3.54) for end points combined. Third, in in vitro studies cellular localization of plakophilin-2, plakoglobin, connexin-43, or N-cadherin were similar in cells transfected with wild-type or mutant plakophilin-2. In conclusion, combining epidemiological data, with data on patients referred for genetic testing for ARVC or HCM/DCM, and data from in vitro studies, PKP2 c.419C>T did not associate with heart failure, arrhythmias, or premature death, with ARVC or HCM/DCM, or with effects in vitro, suggesting that this is not a disease-causing variant.

KW - Journal Article

U2 - 10.1038/ejhg.2015.171

DO - 10.1038/ejhg.2015.171

M3 - Journal article

C2 - 26264440

VL - 24

SP - 732

EP - 738

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

IS - 5

ER -

ID: 164159628