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Mutational Profiles and Molecular Etiologies of Hypertrophic Cardiomyopathy and Dilated Cardiomyopathy in Asian Populations

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Frontiers in Cardiovascular Health

Part of the book series: Progress in Experimental Cardiology ((PREC,volume 9))

Summary

Idiopathic cardiomyopathy (ICM) had been defined as the cardiac disease of unknown etiology. There are two major clinical phenotypes of ICM; hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). During the last decade, a considerable progress has been made for identifying gene mutations as the causes of HCM and DCM. We have searched for mutations in the known disease genes for ICM in Japanese and Korean patients with HCM or DCM, and identified a considerable number of disease-related mutations in a portion of HCM patients and a few DCM patients. In addition, our recent candidate gene approach has revealed that mutations in the titin gene cause both HCM and DCM, and functional analyses of the titin mutations have suggested that the HCM-related and DCM-related mutations would lead to stiff sarcomere and loose sarcomere, respectively. The notion that HCM is a disease of stiff sarcomere can also be supported by that most of the HCM-related mutations in the genes for sarcomeric proteins increase the calcium sensitivity of muscle contraction, i.e. cardiac muscles are contracted under relatively low calcium concentration. In other words, HCM-related sarcomere mutations may lead to relatively stiff sarcomere under physiological condition. On the other hand, most of the DCM-related mutations in Z-disc elements would manifest with loose sarcomere, which may lead to relatively inefficient transmission of power through the Z-disc, then, DCM at least in part can be considered as a disease of loose sarcomere. In this concept, cardiac hypertrophy in HCM can also be considered as compensatory response against the excess overload, and the decompensation could be occurred later, while DCM can be considered as to be with less compensatory hypertrophy and earlier decompensation than HCM.

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Authors and Affiliations

  1. Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10, Kandasurugadai, Chiyoda-ku, Tokyo, 101-0062, Japan

    Akinori Kimura M.D. Ph.D., Manatsu Ito-Satoh, Takeharu Hayashi, Megumi Takahashi, Takuro Arimura & Michio Yasunami

  2. Cardiology Division, Cardiovascular Institute, Samsung Seoul Hospital, Sungkyunkwan University School of Medicine, Seoul, 135-230, Korea

    Su Yeoun Lee, Tae Hong Hwang, Won-Ha Lee & Jeong-Euy Park

Authors
  1. Akinori Kimura M.D. Ph.D.
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  2. Manatsu Ito-Satoh
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  3. Takeharu Hayashi
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  4. Megumi Takahashi
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  5. Takuro Arimura
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  6. Michio Yasunami
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  7. Su Yeoun Lee
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  8. Tae Hong Hwang
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Correspondence to Akinori Kimura M.D. Ph.D. .

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Editors and Affiliations

  1. Institute of Cardiovascular Sciences St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla PhD, MD (Hon), DSc (Hon) (Distinguished Professor and Director), H. Ivan Berkowitz MBA (Consultant) & Pawan K. Singal PhD, DSc (Professor) (Distinguished Professor and Director),  (Consultant) &  (Professor)

  2. Institute of Circulatory & Respiratory Health, Canadian Institutes of Health Research, Vancouver, Canada

    Arun Chockalingam PhD (Assistant Director) (Assistant Director)

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Kimura, A. et al. (2003). Mutational Profiles and Molecular Etiologies of Hypertrophic Cardiomyopathy and Dilated Cardiomyopathy in Asian Populations. In: Dhalla, N.S., Chockalingam, A., Berkowitz, H.I., Singal, P.K. (eds) Frontiers in Cardiovascular Health. Progress in Experimental Cardiology, vol 9. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0455-9_15

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  • DOI: https://doi.org/10.1007/978-1-4615-0455-9_15

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5085-9

  • Online ISBN: 978-1-4615-0455-9

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