1. ¹Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan
2. ²Department of Cardiovascular Medicine, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
3. ³Department of Internal Medicine and Cardiology, Osaka City University School of Medicine, Osaka, Japan
4. ⁴Department of Cardiovascular Medicine, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, Japan

Correspondence: Professor J Azuma, Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan. E-mail: azuma@phs.osaka-u.ac.jp

Received 17 October 2006; Revised 18 January 2007; Accepted 16 February 2007; Published online 3 April 2007.

Abstract

Recent clinical trials have clearly demonstrated that the administration with -blockers decreases the mortality in the patients with chronic heart failure (CHF). However, significant heterogeneity exists in the effectiveness of -blockers among individual cases. We focused on 39 polymorphisms in 16 genes related to adrenergic system and investigated their association with the response to -blockers among 80 patients with CHF owing to idiopathic dilated cardiomyopathy. The polymorphisms of NET T-182C (P=0.019), ADRA1D T1848A (P=0.023) and ADRA1D A1905G (P=0.029) were associated with the improvement of left ventricular fractional shortening (LVFS) by -blockers. Furthermore, combined genotype analysis of NET T-182C and ADRA1D T1848A revealed a significant difference in LVFS improvement among genotype groups (P=0.011). These results suggest that NET (T-182C) and ADRA1D (T1848A and A1905G) polymorphisms are predictive markers of the response to -blockers. Genotyping of these polymorphisms may provide clinical insights into an individual difference in the response to the -blocker therapy in CHF.