Better identification of patients who benefit from implantable cardioverter defibrillators by genotyping the G protein β3 subunit (GNB3) C825T polymorphism.

There is a need for better identification of patients at high risk for malignant arrhythmias who would benefit from implantable cardioverter defibrillators (ICD). The purpose of this study was to assess whether the C825T polymorphism in the G-protein beta3 subunit gene, GNB3, might serve as a genetic marker for recurrent ventricular arrhythmias. Genotyping was performed in 82 patients with ischemic heart disease treated with an ICD for primary and secondary prevention of cardiac arrhythmias. The Kaplan–Meier method was used to estimate the probability of remaining free from VT/VF with cycle length (CL) < 330 ms that required treatment by the ICD. Genotyping yielded 7 individuals homozygous for the 825T allele (TT), 36 homozygous for the C825 allele (CC), and 39 heterozygotes (CT). Multivariate analysis revealed that the C825T polymorphism ( P=0.004), left ventricular ejection fraction ( P=0.009), and QRS-duration ( P=0.039) were independent determinants of severe ventricular arrhythmias. Homozygous carriers of the C825 allele had a 3.9-fold risk for severe ventricular arrhythmias. The results from this pilot study suggest that the C825T polymorphism may have a modifying effect on the propensity towards life-threatening arrhythmias. Genotyping the C825T polymorphism may help to better identify individuals at high risk for life-threatening arrhythmias who benefit from ICD therapy. [ABSTRACT FROM AUTHOR]