Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy

Takeharu Hayashi, Takuro Arimura, Manatsu Itoh-Satoh, Kazuo Ueda, Shigeru Hohda, Natsuko Inagaki, Megumi Takahashi, Hisae Hori, Michio Yasunami, Hirofumi Nishi, Yoshinori Koga, Hiroshi Nakamura, Masunori Matsuzaki, Bo Yoon Choi, Sung Won Bae, Cheol Woon You, Kyung Hoon Han, Jeong Euy Park, Ralph Knöll, Masahiko HoshijimaKenneth R. Chien, Akinori Kimura

Research output: Contribution to journalArticle

203 Citations (Scopus)

Abstract

We sought to explore the relationship between a Tcap gene (TCAP) abnormality and cardiomyopathy. Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) cause severe heart failure and sudden death. Recent genetic investigations have revealed that mutations of genes encoding Z-disc components, including titin and muscle LIM protein (MLP), are the primary cause of both HCM and DCM. The Z-disc plays a role in establishing the mechanical coupling of sarcomeric contraction and stretching, with the titin/Tcap/MLP complex serving as a mechanical stretch sensor. Tcap interacts with the calsarcin, which tethers the calcineurin to the Z-disc. The TCAP was analyzed in 346 patients with HCM (236 familial and 110 sporadic cases) and 136 patients with DCM (34 familial and 102 sporadic cases). Two different in vitro qualitative assays - yeast two-hybrid and glutathion S-transferase pull-down competition - were performed in order to investigate functional changes in Tcap's interaction with MLP, titin, and calsarcin-1 caused by the identified mutations and a reported DCM-associated mutation, R87Q. Two TCAP mutations, T137I and R153H, were found in patients with HCM, and another TCAP mutation, E132Q, was identified in a patient with DCM. It was demonstrated by the qualitative assays that the HCM-associated mutations augment the ability of Tcap to interact with titin and calsarcin-1, whereas the DCM-associated mutations impair the interaction of Tcap with MLP, titin, and calsarcin-1. These observations suggest that the difference in clinical phenotype (HCM or DCM) may be correlated with the property of altered binding among the Z-disc components.

Original languageEnglish
Pages (from-to)2192-2201
Number of pages10
JournalJournal of the American College of Cardiology
Volume44
Issue number11
DOIs
Publication statusPublished - 2004 Dec 7
Externally publishedYes

Fingerprint

Hypertrophic Cardiomyopathy
Dilated Cardiomyopathy
Connectin
Mutation
Genes
Familial Hypertrophic Cardiomyopathy
Two-Hybrid System Techniques
Calcineurin
Sudden Death
Glutathione Transferase
Cardiomyopathies
Heart Failure
Phenotype
2,2,2',4'-tetrachloroacetophenone
cysteine and glycine-rich protein 3

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Hayashi, T., Arimura, T., Itoh-Satoh, M., Ueda, K., Hohda, S., Inagaki, N., ... Kimura, A. (2004). Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy. Journal of the American College of Cardiology, 44(11), 2192-2201. https://doi.org/10.1016/j.jacc.2004.08.058

Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy. / Hayashi, Takeharu; Arimura, Takuro; Itoh-Satoh, Manatsu; Ueda, Kazuo; Hohda, Shigeru; Inagaki, Natsuko; Takahashi, Megumi; Hori, Hisae; Yasunami, Michio; Nishi, Hirofumi; Koga, Yoshinori; Nakamura, Hiroshi; Matsuzaki, Masunori; Choi, Bo Yoon; Bae, Sung Won; You, Cheol Woon; Han, Kyung Hoon; Park, Jeong Euy; Knöll, Ralph; Hoshijima, Masahiko; Chien, Kenneth R.; Kimura, Akinori.

In: Journal of the American College of Cardiology, Vol. 44, No. 11, 07.12.2004, p. 2192-2201.

Research output: Contribution to journalArticle

Hayashi, T, Arimura, T, Itoh-Satoh, M, Ueda, K, Hohda, S, Inagaki, N, Takahashi, M, Hori, H, Yasunami, M, Nishi, H, Koga, Y, Nakamura, H, Matsuzaki, M, Choi, BY, Bae, SW, You, CW, Han, KH, Park, JE, Knöll, R, Hoshijima, M, Chien, KR & Kimura, A 2004, 'Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy', Journal of the American College of Cardiology, vol. 44, no. 11, pp. 2192-2201. https://doi.org/10.1016/j.jacc.2004.08.058
Hayashi, Takeharu ; Arimura, Takuro ; Itoh-Satoh, Manatsu ; Ueda, Kazuo ; Hohda, Shigeru ; Inagaki, Natsuko ; Takahashi, Megumi ; Hori, Hisae ; Yasunami, Michio ; Nishi, Hirofumi ; Koga, Yoshinori ; Nakamura, Hiroshi ; Matsuzaki, Masunori ; Choi, Bo Yoon ; Bae, Sung Won ; You, Cheol Woon ; Han, Kyung Hoon ; Park, Jeong Euy ; Knöll, Ralph ; Hoshijima, Masahiko ; Chien, Kenneth R. ; Kimura, Akinori. / Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy. In: Journal of the American College of Cardiology. 2004 ; Vol. 44, No. 11. pp. 2192-2201.
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AU - Hohda, Shigeru

AU - Inagaki, Natsuko

AU - Takahashi, Megumi

AU - Hori, Hisae

AU - Yasunami, Michio

AU - Nishi, Hirofumi

AU - Koga, Yoshinori

AU - Nakamura, Hiroshi

AU - Matsuzaki, Masunori

AU - Choi, Bo Yoon

AU - Bae, Sung Won

AU - You, Cheol Woon

AU - Han, Kyung Hoon

AU - Park, Jeong Euy

AU - Knöll, Ralph

AU - Hoshijima, Masahiko

AU - Chien, Kenneth R.

AU - Kimura, Akinori

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