DISCOVERY/OREGON SUDS: Polymorphism in the GNAS Gene Predicts Ventricular Tachyarrhythmias and SCD

A gene associated with sudden cardiac death in the general population has been identified using implantable cardioverter defibrillator (ICD) monitoring, and may predict ventricular tachyarrhythmias and sudden cardiac death, according to results from the DISCOVERY trial and Oregon Sudden Death Study presented Aug. 31 during ESC Congress 2015 in London.

In the DISCOVERY trial, which looked at 1,145 patients who received an ICD for primary prevention of sudden cardiac death, ICDs were used to monitor and store cardiac arrhythmia data to study whether specific genes were associated with an increased risk of ventricular tachyarrhythmias. Researchers genotyped seven single nucleotide polymorphisms (SNPs) in three genes (GNB3, GNAQ and GNAS) coding G-protein subunits. The genes found to be associated with cardiac arrhythmias in the DISCOVERY trial were then evaluated in 1,335 patients from Oregon Sudden Death Study, a community-based study analysing causes of sudden cardiac death in the Portland, OR, area.

According to study investigators, 297 patients in the DISCOVERY trial had a ventricular tachyarrhythmia. In univariate analysis, genotypes of two SNPs in the GNAS gene were significantly predictive of ventricular tachyarrhythmias. The increased risk remained significant after adjustment for non-genetic covariates. One of these SNPs, GNAS c.393C>T, was found to be significantly associated with sudden cardiac death in the Oregon Sudden Death Study under the additive and recessive genetic models.

"Using ICD monitoring and a sample of sudden cardiac death patients from the community we found that a polymorphism in the GNAS gene predicts ventricular tachyarrhythmias and sudden cardiac death," said Heiner Wieneke, MD, of the Contilia Heart and Vessel Centre, St. Marien-Hospital Mülheim, Germany. "Our results suggest that GNAS mediated signal transduction may have an important role in ventricular arrhythmogenesis." Going forward, he notes the findings may help to identify patients at increased risk of sudden cardiac death.

"While the results are provocative, validation of these findings on one or preferably more independent cohorts of patients is necessary before this might become part of our diagnostic evaluations," said Kim A. Eagle, MD, MACC, editor-in-chief of

Clinical Topics: Arrhythmias and Clinical EP, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: ESC Congress, Arrhythmias, Cardiac, Death, Sudden, Cardiac, Defibrillators, Implantable, Genotype, Heart Conduction System, Models, Genetic, Polymorphism, Single Nucleotide, Primary Prevention, Protein Subunits, Protein Subunits, Tachycardia, Ventricular

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