Polymorphisms in the GNAS gene as predictors of ventricular tachyarrhythmias and sudden cardiac death: Results from the DISCOVERY Trial and Oregon Sudden Unexpected Death Study

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Standard

Polymorphisms in the GNAS gene as predictors of ventricular tachyarrhythmias and sudden cardiac death : Results from the DISCOVERY Trial and Oregon Sudden Unexpected Death Study. / Wieneke, Heinrich; Svendsen, Jesper Hastrup; Lande, Jeffrey; Spencker, Sebastian; Martinez, Juan Gabriel; Strohmer, Bernhard; Toivonen, Lauri; Le Marec, Hervé; Javier Garcia-Fernandez, F.; Corrado, Domenico; Huertas-Vazquez, Adriana; Uy-Evanado, Audrey; Rusinaru, Carmen; Reinier, Kyndaron; Foldesi, Csaba; Hulak, Wieslaw; Chugh, Sumeet S; Siffert, Winfried.

I: Journal of the American Heart Association, Bind 5, Nr. 12, e003905, 2016.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Wieneke, H, Svendsen, JH, Lande, J, Spencker, S, Martinez, JG, Strohmer, B, Toivonen, L, Le Marec, H, Javier Garcia-Fernandez, F, Corrado, D, Huertas-Vazquez, A, Uy-Evanado, A, Rusinaru, C, Reinier, K, Foldesi, C, Hulak, W, Chugh, SS & Siffert, W 2016, 'Polymorphisms in the GNAS gene as predictors of ventricular tachyarrhythmias and sudden cardiac death: Results from the DISCOVERY Trial and Oregon Sudden Unexpected Death Study', Journal of the American Heart Association, bind 5, nr. 12, e003905. https://doi.org/10.1161/JAHA.116.003905

APA

Wieneke, H., Svendsen, J. H., Lande, J., Spencker, S., Martinez, J. G., Strohmer, B., Toivonen, L., Le Marec, H., Javier Garcia-Fernandez, F., Corrado, D., Huertas-Vazquez, A., Uy-Evanado, A., Rusinaru, C., Reinier, K., Foldesi, C., Hulak, W., Chugh, S. S., & Siffert, W. (2016). Polymorphisms in the GNAS gene as predictors of ventricular tachyarrhythmias and sudden cardiac death: Results from the DISCOVERY Trial and Oregon Sudden Unexpected Death Study. Journal of the American Heart Association, 5(12), [e003905]. https://doi.org/10.1161/JAHA.116.003905

Vancouver

Wieneke H, Svendsen JH, Lande J, Spencker S, Martinez JG, Strohmer B o.a. Polymorphisms in the GNAS gene as predictors of ventricular tachyarrhythmias and sudden cardiac death: Results from the DISCOVERY Trial and Oregon Sudden Unexpected Death Study. Journal of the American Heart Association. 2016;5(12). e003905. https://doi.org/10.1161/JAHA.116.003905

Author

Wieneke, Heinrich ; Svendsen, Jesper Hastrup ; Lande, Jeffrey ; Spencker, Sebastian ; Martinez, Juan Gabriel ; Strohmer, Bernhard ; Toivonen, Lauri ; Le Marec, Hervé ; Javier Garcia-Fernandez, F. ; Corrado, Domenico ; Huertas-Vazquez, Adriana ; Uy-Evanado, Audrey ; Rusinaru, Carmen ; Reinier, Kyndaron ; Foldesi, Csaba ; Hulak, Wieslaw ; Chugh, Sumeet S ; Siffert, Winfried. / Polymorphisms in the GNAS gene as predictors of ventricular tachyarrhythmias and sudden cardiac death : Results from the DISCOVERY Trial and Oregon Sudden Unexpected Death Study. I: Journal of the American Heart Association. 2016 ; Bind 5, Nr. 12.

Bibtex

@article{2d19c6e2bef54f918339471511938586,
title = "Polymorphisms in the GNAS gene as predictors of ventricular tachyarrhythmias and sudden cardiac death: Results from the DISCOVERY Trial and Oregon Sudden Unexpected Death Study",
abstract = "Background--Population-based studies suggest that genetic factors contribute to sudden cardiac death (SCD). Methods and Results--In the first part of the present study (Diagnostic Data Influence on Disease Management and Relation of Genetic Polymorphisms to Ventricular Tachy-arrhythmia in ICD Patients [DISCOVERY] trial) Cox regression was done to determine if 7 single-nucleotide polymorphisms (SNPs) in 3 genes coding G-protein subunits (GNB3, GNAQ, GNAS) were associated with ventricular tachyarrhythmia (VT) in 1145 patients receiving an implantable cardioverter-defibrillator (ICD). In the second part of the study, SNPs significantly associated with VT were further investigated in 1335 subjects from the Oregon SUDS, acommunity-based study analyzing causes of SCD. In the DISCOVERY trial, genotypes of 2 SNPs in the GNAS gene were nominally significant in the prospective screening and significantly associated with VT when viewed as recessive traits in post hoc analyses (TT vs CC/CT in c.393C>T: HR 1.42 [CI 1.11- 1.80], P=0.005; TT vs CC/CT in c.2273C>T: HR 1.57 [CI 1.18-2.09], P=0.002). TT genotype in either SNP was associated with a HR of 1.58 (CI 1.26-1.99) (P=0.0001). In the Oregon SUDS cohort significant evidence for association with SCD was observed for GNAS c.393C>T under the additive (P=0.039, OR=1.21 [CI 1.05-1.45]) and recessive (P=0.01, OR=1.52 [CI 1.10-2.13]) genetic models. Conclusions--GNAS harbors 2 SNPs that were associated with an increased risk for VT in ICD patients, of which 1 was successfully replicated in a community-based population of SCD cases. To the best of our knowledge, this is the first example of a gene variant identified by ICD VT monitoring as a surrogate parameter for SCD and also confirmed in the general population.",
keywords = "Arrhythmia, G proteins, Implantable cardioverter-defibrillator, Single nucleotide polymorphism, Sudden cardiac death, Ventricular tachycardia arrhythmia",
author = "Heinrich Wieneke and Svendsen, {Jesper Hastrup} and Jeffrey Lande and Sebastian Spencker and Martinez, {Juan Gabriel} and Bernhard Strohmer and Lauri Toivonen and {Le Marec}, Herv{\'e} and {Javier Garcia-Fernandez}, F. and Domenico Corrado and Adriana Huertas-Vazquez and Audrey Uy-Evanado and Carmen Rusinaru and Kyndaron Reinier and Csaba Foldesi and Wieslaw Hulak and Chugh, {Sumeet S} and Winfried Siffert",
year = "2016",
doi = "10.1161/JAHA.116.003905",
language = "English",
volume = "5",
journal = "Journal of the American Heart Association",
issn = "2047-9980",
publisher = "Wiley-Blackwell",
number = "12",

}

RIS

TY - JOUR

T1 - Polymorphisms in the GNAS gene as predictors of ventricular tachyarrhythmias and sudden cardiac death

T2 - Results from the DISCOVERY Trial and Oregon Sudden Unexpected Death Study

AU - Wieneke, Heinrich

AU - Svendsen, Jesper Hastrup

AU - Lande, Jeffrey

AU - Spencker, Sebastian

AU - Martinez, Juan Gabriel

AU - Strohmer, Bernhard

AU - Toivonen, Lauri

AU - Le Marec, Hervé

AU - Javier Garcia-Fernandez, F.

AU - Corrado, Domenico

AU - Huertas-Vazquez, Adriana

AU - Uy-Evanado, Audrey

AU - Rusinaru, Carmen

AU - Reinier, Kyndaron

AU - Foldesi, Csaba

AU - Hulak, Wieslaw

AU - Chugh, Sumeet S

AU - Siffert, Winfried

PY - 2016

Y1 - 2016

N2 - Background--Population-based studies suggest that genetic factors contribute to sudden cardiac death (SCD). Methods and Results--In the first part of the present study (Diagnostic Data Influence on Disease Management and Relation of Genetic Polymorphisms to Ventricular Tachy-arrhythmia in ICD Patients [DISCOVERY] trial) Cox regression was done to determine if 7 single-nucleotide polymorphisms (SNPs) in 3 genes coding G-protein subunits (GNB3, GNAQ, GNAS) were associated with ventricular tachyarrhythmia (VT) in 1145 patients receiving an implantable cardioverter-defibrillator (ICD). In the second part of the study, SNPs significantly associated with VT were further investigated in 1335 subjects from the Oregon SUDS, acommunity-based study analyzing causes of SCD. In the DISCOVERY trial, genotypes of 2 SNPs in the GNAS gene were nominally significant in the prospective screening and significantly associated with VT when viewed as recessive traits in post hoc analyses (TT vs CC/CT in c.393C>T: HR 1.42 [CI 1.11- 1.80], P=0.005; TT vs CC/CT in c.2273C>T: HR 1.57 [CI 1.18-2.09], P=0.002). TT genotype in either SNP was associated with a HR of 1.58 (CI 1.26-1.99) (P=0.0001). In the Oregon SUDS cohort significant evidence for association with SCD was observed for GNAS c.393C>T under the additive (P=0.039, OR=1.21 [CI 1.05-1.45]) and recessive (P=0.01, OR=1.52 [CI 1.10-2.13]) genetic models. Conclusions--GNAS harbors 2 SNPs that were associated with an increased risk for VT in ICD patients, of which 1 was successfully replicated in a community-based population of SCD cases. To the best of our knowledge, this is the first example of a gene variant identified by ICD VT monitoring as a surrogate parameter for SCD and also confirmed in the general population.

AB - Background--Population-based studies suggest that genetic factors contribute to sudden cardiac death (SCD). Methods and Results--In the first part of the present study (Diagnostic Data Influence on Disease Management and Relation of Genetic Polymorphisms to Ventricular Tachy-arrhythmia in ICD Patients [DISCOVERY] trial) Cox regression was done to determine if 7 single-nucleotide polymorphisms (SNPs) in 3 genes coding G-protein subunits (GNB3, GNAQ, GNAS) were associated with ventricular tachyarrhythmia (VT) in 1145 patients receiving an implantable cardioverter-defibrillator (ICD). In the second part of the study, SNPs significantly associated with VT were further investigated in 1335 subjects from the Oregon SUDS, acommunity-based study analyzing causes of SCD. In the DISCOVERY trial, genotypes of 2 SNPs in the GNAS gene were nominally significant in the prospective screening and significantly associated with VT when viewed as recessive traits in post hoc analyses (TT vs CC/CT in c.393C>T: HR 1.42 [CI 1.11- 1.80], P=0.005; TT vs CC/CT in c.2273C>T: HR 1.57 [CI 1.18-2.09], P=0.002). TT genotype in either SNP was associated with a HR of 1.58 (CI 1.26-1.99) (P=0.0001). In the Oregon SUDS cohort significant evidence for association with SCD was observed for GNAS c.393C>T under the additive (P=0.039, OR=1.21 [CI 1.05-1.45]) and recessive (P=0.01, OR=1.52 [CI 1.10-2.13]) genetic models. Conclusions--GNAS harbors 2 SNPs that were associated with an increased risk for VT in ICD patients, of which 1 was successfully replicated in a community-based population of SCD cases. To the best of our knowledge, this is the first example of a gene variant identified by ICD VT monitoring as a surrogate parameter for SCD and also confirmed in the general population.

KW - Arrhythmia

KW - G proteins

KW - Implantable cardioverter-defibrillator

KW - Single nucleotide polymorphism

KW - Sudden cardiac death

KW - Ventricular tachycardia arrhythmia

U2 - 10.1161/JAHA.116.003905

DO - 10.1161/JAHA.116.003905

M3 - Journal article

C2 - 27895044

AN - SCOPUS:85006467112

VL - 5

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

SN - 2047-9980

IS - 12

M1 - e003905

ER -

ID: 180790051