Abstract

Dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are genetically and phenotypically heterogeneous. Cardiac function is improved after treatment in some cardiomyopathy patients, but little is known about genetic predictors of long-term outcomes and myocardial recovery following medical treatment. To elucidate the genetic basis of cardiomyopathy in Japan and the genotypes involved in prognosis and left ventricular reverse remodeling (LVRR), we performed targeted sequencing on 120 DCM (70 sporadic and 50 familial) and 52 HCM (15 sporadic and 37 familial) patients and integrated their genotypes with clinical phenotypes. Among the 120 DCM patients, 20 (16.7%) had TTN truncating variants and 13 (10.8%) had LMNA variants. TTN truncating variants were the major cause of sporadic DCM (21.4% of sporadic cases) as with Caucasians, whereas LMNA variants, which include a novel recurrent LMNA E115M variant, were the most frequent in familial DCM (24.0% of familial cases) unlike Caucasians. Of the 52 HCM patients, MYH7 and MYBPC3 variants were the most common (12 (23.1%) had MYH7 variants and 11 (21.2%) had MYBPC3 variants) as with Caucasians. DCM patients harboring TTN truncating variants had better prognosis than those with LMNA variants. Most patients with TTN truncating variants achieved LVRR, unlike most patients with LMNA variants.

Details

Title
Genetic basis of cardiomyopathy and the genotypes involved in prognosis and left ventricular reverse remodeling
Author
Tobita, Takashige 1 ; Nomura, Seitaro 2 ; Fujita, Takanori 3 ; Morita, Hiroyuki 4 ; Asano, Yoshihiro 5 ; Onoue, Kenji 6 ; Ito, Masamichi 4 ; Imai, Yasushi 7 ; Suzuki, Atsushi 8 ; Ko, Toshiyuki 4 ; Satoh, Masahiro 9 ; Fujita, Kanna 4 ; Naito, Atsuhiko T 4 ; Furutani, Yoshiyuki 10 ; Toko, Haruhiro 4 ; Harada, Mutsuo 4 ; Eisuke Amiya 4   VIAFID ORCID Logo  ; Hatano, Masaru 4 ; Takimoto, Eiki 4 ; Shiga, Tsuyoshi 8 ; Nakanishi, Toshio 10 ; Sakata, Yasushi 5 ; Ono, Minoru 11 ; Saito, Yoshihiko 6 ; Takashima, Seiji 12 ; Hagiwara, Nobuhisa 8 ; Aburatani, Hiroyuki 3   VIAFID ORCID Logo  ; Komuro, Issei 4 

1  Department of Cardiology, Tokyo Women’s Medical University, Tokyo, Japan; Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan 
2  Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan; Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan 
3  Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan 
4  Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan 
5  Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan 
6  First Department of Internal Medicine, Nara Medical University, Kashihara, Japan 
7  Division of Cardiovascular Medicine, Jichi Medical University, Shimotsuke, Japan 
8  Department of Cardiology, Tokyo Women’s Medical University, Tokyo, Japan 
9  Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan 
10  Department of Pediatric Cardiology, Tokyo Women’s Medical University, Tokyo, Japan 
11  Department of Cardiovascular Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan 
12  Department of Medical Biochemistry, Osaka University Graduate School of Medicine, Osaka, Japan 
Pages
1-11
Publication year
2018
Publication date
Jan 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-018-20114-9
ProQuest document ID
1992990628
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.