Abstract 2911: T-182C Polymorphism in the Norepinephrine Transporter Gene (SLC6A2) and Risk of Cardiovascular Events in Patients with Dilated Cardiomyopathy: Association of the T allele with a Reduced Risk for Cardiovascular Events
Backgrounds: The increase in sympathetic activity is one of the hallmarks of the chronic heart failure and has been shown to have an important impact on survival in patients with dilated cardiomyopathy (DCM). Norepinephrine transporter (NET) recaptures as much as 90% of released norepinephrine in the heart, making it a critical mediator of norepinephrine inactivation and presynaptic catecholamine homeostasis. Recently, the polymorphism of NET T-182C was reported to be associated with the improvement of left ventricular systolic function by beta-blockers in patients with DCM. However, the association between the incidence of cardiovascular events and the NET polymorphism in patients DCM has not been understood. The purpose of this study was to evaluate the effect of this polymorphism on the incidence of cardiovascular events in patients with DCM.
Methods: Eighty-three genetically unrelated patients with nonfamilial DCM (64 males, mean age at initial clinical evaluation 59 ± 14 years) were enrolled in this study. An adverse cardiovascular event was defined as cardiac death or hospitalization for cardiac reasons. The time to the first adverse cardiovascular event was analyzed by the Kaplan-Meier method. The TaqMan polymerase chain reaction method was used for the determination of genotypes of the NET T-182C gene (SLC6A2) (rs#2242446).
Results: The distribution of the NET T-182C genotypes (T/T, T/C, and C/C) was 43%, 45%, and 12%, respectively. The NET T-182C T allele frequency was 0.63. During a mean follow-up period of 45 months, 20 cardiovascular events had occurred. Eight patients died from cardiac cause (1 from pump failure and 7 from sudden cardiac death) and there were 12 hospitalizations for new onset or worsening of heart failure symptoms. The cardiovascular event rate of the patients carrying the T allele (T/T and T/C genotype, n = 73) was significantly lower than that of the patients not carrying the T allele (C/C genotype, n = 10) (p = 0.03).
Conclusion: Our data suggested that the T allele of the NET T-182C gene may be a protective factor against cardiovascular events in patients with DCM.