Inoue Shunsuke, Ko Toshiyuki, Shindo Akito, Nomura Seitaro, Yamada Takanobu, Jimba Takahiro, Dai Zhehao, Nakao Harumi, Suzuki Atsushi, Kashimura Takeshi, Iwahana Togo, Goto Keiko, Matsushima Shouji, Ishida Junichi, Amiya Eisuke, Zhang Bo, Kubota Masayuki, Sawami Kosuke, Heryed Tuolisi, Yamada Shintaro, Katoh Manami, Katagiri Mikako, Ito Masamichi, Nayakama Yukiteru, Fujiu Katsuhito, Hatano Masaru, Takeda Norifumi, Takimoto Eiki, Akazawa Hiroshi, Morita Hiroyuki, Yamaguchi Junichi, Inomata Takayuki, Kobayashi Yoshio, Minamino Tohru, Tsutsui Hiroyuki, Kurokawa Mineo, Aiba Atsu, Aburatani Hiroyuki, Komuro Issei
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
JACC Basic Transl Sci. 2024 Jun 12;9(8):956-967. doi: 10.1016/j.jacbts.2024.04.010. eCollection 2024 Aug.
Although clonal hematopoiesis of indeterminate potential (CHIP) is an adverse prognostic factor for atherosclerotic disease, its impact on nonischemic dilated cardiomyopathy (DCM) is elusive. The authors performed whole-exome sequencing and deep target sequencing among 198 patients with DCM and detected germline mutations in cardiomyopathy-related genes and somatic mutations in CHIP driver genes. Twenty-five CHIP driver mutations were detected in 22 patients with DCM. Ninety-two patients had cardiomyopathy-related pathogenic mutations. Multivariable analysis revealed that CHIP was an independent risk factor of left ventricular reverse remodeling, irrespective of known prognostic factors. CHIP exacerbated cardiac systolic dysfunction and fibrosis in a DCM murine model. The identification of germline and somatic mutations in patients with DCM predicts clinical prognosis.
尽管不确定潜能的克隆性造血（CHIP）是动脉粥样硬化性疾病的不良预后因素，但其对非缺血性扩张型心肌病（DCM）的影响尚不清楚。作者对198例DCM患者进行了全外显子组测序和深度靶向测序，检测到心肌病相关基因的胚系突变和CHIP驱动基因的体细胞突变。在22例DCM患者中检测到25个CHIP驱动突变。92例患者有心肌病相关的致病突变。多变量分析显示，无论已知的预后因素如何，CHIP都是左心室逆向重构的独立危险因素。CHIP在DCM小鼠模型中加剧了心脏收缩功能障碍和纤维化。DCM患者中胚系和体细胞突变的鉴定可预测临床预后。
