Polymorphisms of norepinephrine transporter and adrenergic receptor alpha1D are associated with the response to beta-blockers in dilated cardiomyopathy.
Recent clinical trials have clearly demonstrated that the administration with beta-blockers decreases the mortality in the patients with chronic heart failure (CHF). However, significant heterogeneity exists in the effectiveness of beta-blockers among individual cases. We focused on 39 polymorphisms in 16 genes related to adrenergic system and investigated their association with the response to beta-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 beta-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 beta-blockers. Genotyping of these polymorphisms may provide clinical insights into an individual difference in the response to the beta-blocker therapy in CHF.
Nonen
S
S
Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka, Japan.
Okamoto
H
H
Fujio
Y
Y
Takemoto
Y
Y
Yoshiyama
M
M
Hamaguchi
T
T
Matsui
Y
Y
Yoshikawa
J
J
Kitabatake
A
A
Azuma
J
J
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000368:Aged; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C547719:ADRA1D protein, human; D000319:Adrenergic beta-Antagonists; D050484:Norepinephrine Plasma Membrane Transport Proteins; D018340:Receptors, Adrenergic, alpha-1