Abstract 2298: Beta2-Adrenoceptor Gene Variant Arg16Gly is Associated With Idiopathic Ventricular Outflow-tract Tachycardia
Introduction: The imbalance of sympathetic nervous system was involved in the pathogenesis of idiopathic ventricular outflow-tract tachycardia (IVOT). We aimed to investigate whether major single nucleotide polymorphisms (SNPs) in β1 and β2-adrenoceptors and GNB3 C825T were associated with IVOT and verapamil sensitive idiopathic left ventricular tachycardia (ILVT).
Methods and Results: A total of 227 IVOT patients and 110 ILVT patients were consecutively enrolled into this study. 634 controls were randomly selected from the corresponding group. The clinical characteristics of the two subtypes of idiopathic ventricular arrhythmias were significantly different: Compared to ILVT, IVOT occurred at an older age (38.2 ± 13.9 years vs. 32.5 ± 14.4 years, P < 0.001) and in more females (60.8% vs. 31.8%, P < 0.001). The initial episode of ventricular tachycardia provocated at sympathetic nervous activation state more frequently in IVOT than in ILVT (76.7% vs. 41.8%, P < 0.001). On the presentation of index clinical arrhythmia, 78.0% patients of IVOT presented with frequent premature ventricular contractions with or without repetitive nonsustained ventricular tachycardia, while 73.6% patients of ILVT presented with paroxysmal sustained monomorphic ventricular tachycardia or nonsustained ventricular tachycardia (P < 0.001). SNPs analysis revealed that IVOT patients had higher frequency of Gly16Gly genotype and Gly16 allele in β2-adrenoceptor compared with controls (24.7% vs. 17.8%, P = 0.024; 50.4% vs. 42.4%, P = 0.003). After adjustment for age and gender, IVOT was significantly associated with Arg16Gly (OR = 1.62, 95% CI of OR = 1.14 –2.30, P = 0.008), and Gly16Gln27 haplotype was a risk factor of IVOT (OR = 1.38, 95% CI of OR = 1.11–1.73, P = 0.012). However, other four SNPs including Ser49Gly, Arg389Gly in β1- adrenoceptor and Gln27Glu in β2-adrenoceptor and GNB3 C825T did not differ between IVOT and controls. In ILVT, no significant difference was found in these five SNPs compared with controls.
Conclusions: Arg16Gly in β2-adrenoceptor is significantly associated with IVOT in Chinese Han population. Major SNPs in β1 and β2-adrenoceptor and GNB3 C825T are not associated with ILVT. These data suggest a different arrhythmogenic mechanism in IVOT and ILVT.