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Polymorphisms of norepinephrine transporter and adrenergic receptor α1D are associated with the response to β-blockers in dilated cardiomyopathy

The Pharmacogenomics Journal volume 8, pages 78–84 (2008)Cite this article

Abstract

Recent clinical trials have clearly demonstrated that the administration with β-blockers decreases the mortality in the patients with chronic heart failure (CHF). However, significant heterogeneity exists in the effectiveness of β-blockers among individual cases. We focused on 39 polymorphisms in 16 genes related to adrenergic system and investigated their association with the response to β-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 β-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 β-blockers. Genotyping of these polymorphisms may provide clinical insights into an individual difference in the response to the β-blocker therapy in CHF.

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Acknowledgements

We acknowledge Dr Tsuyoshi Fukuda and Ms Tomoko Kubota for their stimulating discussions. We thank Dr Mitsuru Sugawara (Department of Pharmacy, Hokkaido University Hospital) for collecting blood samples. We also thank Professor Tatsuya Takagi (Department of Pharmaceutical Information Science, Graduate School of Pharmaceutical Sciences, Osaka University) for helpful discussion about statistics. This study was supported in part by a grant from the Organization for Pharmaceutical Safety and Research (OPSR) in Japan and Grants-in-Aid for Research on Measures for Intractable Diseases from Ministry of Health, Labour and Welfare and for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan. This study was also supported by a grant from the Osaka Medical Research Foundation for Incurable Diseases and from Daiichi Pharmaceutical Co., Ltd.

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Authors and Affiliations

  1. Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan

    S Nonen, Y Fujio & J Azuma

  2. Department of Cardiovascular Medicine, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan

    H Okamoto, Y Matsui & A Kitabatake

  3. Department of Internal Medicine and Cardiology, Osaka City University School of Medicine, Osaka, Japan

    Y Takemoto, M Yoshiyama & J Yoshikawa

  4. Department of Cardiovascular Medicine, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, Japan

    T Hamaguchi

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  1. S Nonen
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  2. H Okamoto
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  9. A Kitabatake
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Corresponding author

Correspondence to J Azuma.

Additional information

Note: A preliminary report of this work was presented at the annual meeting of the Pacific Rim Association for Clinical Pharmacogenetics in Changsha, China, 28–30 June, 2006.

Duality of Interest

The authors declared no duality of interest.

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Nonen, S., Okamoto, H., Fujio, Y. et al. Polymorphisms of norepinephrine transporter and adrenergic receptor α1D are associated with the response to β-blockers in dilated cardiomyopathy. Pharmacogenomics J 8, 78–84 (2008). https://doi.org/10.1038/sj.tpj.6500450

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