Journal article
Rare variants in genes encoding MuRF1 and MuRF2 are modifiers of hypertrophic cardiomyopathy
International journal of molecular sciences, Vol.15(6), pp.9302-9313
05/26/2014
DOI: 10.3390/ijms15069302
PMCID: PMC4100095
PMID: 24865491
Abstract
Modifier genes contribute to the diverse clinical manifestations of hypertrophic cardiomyopathy (HCM), but are still largely unknown. Muscle ring finger (MuRF) proteins are a class of muscle-specific ubiquitin E3-ligases that appear to modulate cardiac mass and function by regulating the ubiquitin-proteasome system. In this study we screened all the three members of the MuRF family, MuRF1, MuRF2 and MuRF3, in 594 unrelated HCM patients and 307 healthy controls by targeted resequencing. Identified rare variants were confirmed by capillary Sanger sequencing. The prevalence of rare variants in both MuRF1 and MuRF2 in HCM patients was higher than that in control subjects (MuRF1 13/594 (2.2%) vs. 1/307 (0.3%), p = 0.04; MuRF2 22/594 (3.7%) vs. 2/307 (0.7%); p = 0.007). Patients with rare variants in MuRF1 or MuRF2 were younger (p = 0.04) and had greater maximum left ventricular wall thickness (p = 0.006) than those without such variants. Mutations in genes encoding sarcomere proteins were present in 19 (55.9%) of the 34 HCM patients with rare variants in MuRF1 and MuRF2. These data strongly supported that rare variants in MuRF1 and MuRF2 are associated with higher penetrance and more severe clinical manifestations of HCM. The findings suggest that dysregulation of the ubiquitin-proteasome system contributes to the pathogenesis of HCM.
Details
- Title: Subtitle
- Rare variants in genes encoding MuRF1 and MuRF2 are modifiers of hypertrophic cardiomyopathy
- Creators
- Ming Su - State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. suming28@163.comJizheng Wang - State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. jzwang@hotmail.comLianming Kang - State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. lianmingkang@126.comYilu Wang - Intensive Care Unit, China Meitan General Hospital, Beijing 100028, China. wangyilu0908@163.comYubao Zou - State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. zouyb1973@gmail.comXinxing Feng - State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. xinxing_feng@hotmail.comDong Wang - State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. wangdongfw@gmail.comFerhaan Ahmad - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA. ferhaan-ahmad@uiowa.eduXianliang Zhou - State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. zhouxianliang0326@hotmail.comRutai Hui - State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. huirutai@gmail.comLei Song - State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. lsongqd@yahoo.com
- Resource Type
- Journal article
- Publication Details
- International journal of molecular sciences, Vol.15(6), pp.9302-9313
- DOI
- 10.3390/ijms15069302
- PMID
- 24865491
- PMCID
- PMC4100095
- NLM abbreviation
- Int J Mol Sci
- ISSN
- 1661-6596
- eISSN
- 1422-0067
- Publisher
- Switzerland
- Grant note
- U01 HL108642 / NHLBI NIH HHS U01HL108642-01 / NHLBI NIH HHS
- Language
- English
- Date published
- 05/26/2014
- Academic Unit
- Radiology; Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984025367102771
Metrics
33 Record Views