• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

富含组氨酸的钙结合蛋白中的Ser96Ala变体与特发性扩张型心肌病中危及生命的室性心律失常有关。

The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy.

作者信息

Arvanitis Demetrios A, Sanoudou Despina, Kolokathis Fotis, Vafiadaki Elizabeth, Papalouka Vasiliki, Kontrogianni-Konstantopoulos Aikaterini, Theodorakis George N, Paraskevaidis Ioannis A, Adamopoulos Stamatios, Dorn Gerald W, Kremastinos Dimitrios Th, Kranias Evangelia G

机构信息

Molecular Biology Division, Biomedical Research Foundation, Academy of Athens, Athens, Greece.

出版信息

Eur Heart J. 2008 Oct;29(20):2514-25. doi: 10.1093/eurheartj/ehn328. Epub 2008 Jul 9.

DOI:10.1093/eurheartj/ehn328
PMID:18617481
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2567024/
Abstract

AIMS

To investigate whether genetic variants of the histidine-rich calcium (HRC)-binding protein are associated with idiopathic dilated cardiomyopathy (DCM) and its progression.

METHODS AND RESULTS

We screened 123 idiopathic DCM patients and 96 healthy individuals by single-strand conformation polymorphism analysis and direct sequencing for genetic variants in HRC. Six polymorphisms were detected: Leu35Leu (A/G), Ser43Asn (G/A), Ser96Ala (T/G), Glu202_Glu203insGlu (-/GAG), Asp261del (GAT/-), and an in-frame insertion of 51 amino acids at His321. The analysis of their frequencies did not reveal any significant correlation with DCM development. However, the Ser96Ala polymorphism exhibited a statistically significant correlation with the occurrence of life-threatening ventricular arrhythmias. During a follow-up of 4.02 +/- 2.4 years, the risk for ventricular arrhythmias was higher (HR, 9.620; 95% CI, 2.183-42.394; P = 0.003) in the Ala/Ala patients, compared with Ser/Ser homozygous patients. On multivariable Cox regression analysis, the Ser96Ala polymorphism was the only significant genetic arrythmogenesis predictor in DCM patients (HR, 4.191; 95% CI, 0.838-20.967; P = 0.018).

CONCLUSION

The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias in idiopathic DCM and may serve as an independent predictor of susceptibility to arrhythmogenesis in the setting of DCM.

摘要

目的

研究富含组氨酸的钙（HRC）结合蛋白的基因变异是否与特发性扩张型心肌病（DCM）及其发展相关。

方法与结果

我们通过单链构象多态性分析和直接测序，对123例特发性DCM患者和96例健康个体进行HRC基因变异筛查。检测到6种多态性：Leu35Leu（A/G）、Ser43Asn（G/A）、Ser96Ala（T/G）、Glu202_Glu203insGlu（-/GAG）、Asp261del（GAT/-）以及His321处51个氨基酸的框内插入。对其频率的分析未发现与DCM发生有任何显著相关性。然而，Ser96Ala多态性与危及生命的室性心律失常的发生具有统计学显著相关性。在4.02±2.4年的随访期间，与Ser/Ser纯合患者相比，Ala/Ala患者发生室性心律失常的风险更高（HR，9.620；95%CI，2.183 - 42.394；P = 0.003）。在多变量Cox回归分析中，Ser96Ala多态性是DCM患者中唯一显著的遗传性心律失常预测因子（HR，4.191；95%CI，0.83 - 20.967；P = 0.018）。

结论

HRC的Ser96Ala基因变异与特发性DCM中危及生命的室性心律失常相关，可能作为DCM情况下心律失常易感性的独立预测因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e99/2638567/6983b3e2335d/ehn32806.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e99/2638567/48ef766302b5/ehn32801.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e99/2638567/720d2907caf4/ehn32802.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e99/2638567/d0a924eb6912/ehn32803.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e99/2638567/6bf693445a51/ehn32804.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e99/2638567/02f5e2a87b00/ehn32805.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e99/2638567/6983b3e2335d/ehn32806.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e99/2638567/48ef766302b5/ehn32801.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e99/2638567/720d2907caf4/ehn32802.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e99/2638567/d0a924eb6912/ehn32803.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e99/2638567/6bf693445a51/ehn32804.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e99/2638567/02f5e2a87b00/ehn32805.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e99/2638567/6983b3e2335d/ehn32806.jpg

相似文献

1
The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy.富含组氨酸的钙结合蛋白中的Ser96Ala变体与特发性扩张型心肌病中危及生命的室性心律失常有关。
Eur Heart J. 2008 Oct;29(20):2514-25. doi: 10.1093/eurheartj/ehn328. Epub 2008 Jul 9.
2
Lack of Evidence for the Role of the p.(Ser96Ala) Polymorphism in Histidine-Rich Calcium Binding Protein as a Secondary Hit in Cardiomyopathies.缺乏证据表明丝氨酸 96 处丙氨酸（Ser96Ala）多态性在富含组氨酸钙结合蛋白中作为心肌病的次要打击的作用。
Int J Mol Sci. 2023 Nov 3;24(21):15931. doi: 10.3390/ijms242115931.
3
Impaired calcium homeostasis is associated with sudden cardiac death and arrhythmias in a genetic equivalent mouse model of the human HRC-Ser96Ala variant.钙稳态失调与人类 HRC-Ser96Ala 变体的基因等效小鼠模型中的心脏性猝死和心律失常有关。
Cardiovasc Res. 2017 Sep 1;113(11):1403-1417. doi: 10.1093/cvr/cvx113.
4
Catecholaminergic-induced arrhythmias in failing cardiomyocytes associated with human HRCS96A variant overexpression.人源 HRCS96A 变异体过表达致衰竭心肌细胞儿茶酚胺诱导性心律失常。
Am J Physiol Heart Circ Physiol. 2011 Oct;301(4):H1588-95. doi: 10.1152/ajpheart.01153.2010. Epub 2011 Jul 8.
5
Abnormal calcium cycling and cardiac arrhythmias associated with the human Ser96Ala genetic variant of histidine-rich calcium-binding protein.与富含组氨酸钙结合蛋白的人类 Ser96Ala 遗传变异相关的异常钙循环和心律失常。
J Am Heart Assoc. 2013 Oct 14;2(5):e000460. doi: 10.1161/JAHA.113.000460.
6
Dilated cardiomyopathy caused by truncating titin variants: long-term outcomes, arrhythmias, response to treatment and sex differences.肌节蛋白截断变异导致的扩张型心肌病：长期结局、心律失常、治疗反应和性别差异。
J Med Genet. 2021 Dec;58(12):832-841. doi: 10.1136/jmedgenet-2020-107178. Epub 2020 Oct 26.
7
Genetic arrhythmias complicating patients with dilated cardiomyopathy.遗传性心律失常并发扩张型心肌病患者。
Heart Rhythm. 2020 Feb;17(2):305-312. doi: 10.1016/j.hrthm.2019.09.012. Epub 2019 Sep 12.
8
Non‑synonymous polymorphisms in the and genes may be associated with all‑cause death in patients with non‑ischemic heart failure.和基因中的非同义多态性可能与非缺血性心力衰竭患者的全因死亡有关。
Exp Ther Med. 2023 Dec 4;27(1):48. doi: 10.3892/etm.2023.12337. eCollection 2024 Jan.
9
Genotype-phenotype associations in dilated cardiomyopathy: meta-analysis on more than 8000 individuals.扩张型心肌病的基因型-表型关联：对8000多名个体的荟萃分析
Clin Res Cardiol. 2017 Feb;106(2):127-139. doi: 10.1007/s00392-016-1033-6. Epub 2016 Aug 30.
10
Natural History of Dilated Cardiomyopathy in Children.儿童扩张型心肌病的自然病史
J Am Heart Assoc. 2016 Jun 30;5(7):e003450. doi: 10.1161/JAHA.116.003450.

引用本文的文献

1
Systematic Review, Meta-Analysis, and Population Study to Determine the Biologic Sex Ratio in Dilated Cardiomyopathy.确定扩张型心肌病生物学性别比例的系统评价、荟萃分析和人群研究
Circulation. 2025 Feb 18;151(7):442-459. doi: 10.1161/CIRCULATIONAHA.124.070872. Epub 2025 Feb 3.
2
FAM20C: A key protein kinase in multiple diseases.FAM20C：多种疾病中的关键蛋白激酶。
Genes Dis. 2023 Nov 23;12(2):101179. doi: 10.1016/j.gendis.2023.101179. eCollection 2025 Mar.
3
Lack of Evidence for the Role of the p.(Ser96Ala) Polymorphism in Histidine-Rich Calcium Binding Protein as a Secondary Hit in Cardiomyopathies.

本文引用的文献

1
Preventing tomorrow's sudden cardiac death today: part I: Current data on risk stratification for sudden cardiac death.从今天开始预防明日的心源性猝死：第一部分：心源性猝死风险分层的当前数据
Am Heart J. 2007 Jun;153(6):941-50. doi: 10.1016/j.ahj.2007.03.003.
2
Histidine-rich Ca-binding protein interacts with sarcoplasmic reticulum Ca-ATPase.富含组氨酸的钙结合蛋白与肌浆网钙ATP酶相互作用。
Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1581-9. doi: 10.1152/ajpheart.00278.2007. Epub 2007 May 25.
3
Histidine-rich Ca binding protein: a regulator of sarcoplasmic reticulum calcium sequestration and cardiac function.
缺乏证据表明丝氨酸 96 处丙氨酸（Ser96Ala）多态性在富含组氨酸钙结合蛋白中作为心肌病的次要打击的作用。
Int J Mol Sci. 2023 Nov 3;24(21):15931. doi: 10.3390/ijms242115931.
4
Targeting calcium regulators as therapy for heart failure: focus on the sarcoplasmic reticulum Ca-ATPase pump.将钙调节因子作为心力衰竭的治疗靶点：聚焦于肌浆网钙ATP酶泵
Front Cardiovasc Med. 2023 Jul 18;10:1185261. doi: 10.3389/fcvm.2023.1185261. eCollection 2023.
5
Aberrant PLN-R14del Protein Interactions Intensify SERCA2a Inhibition, Driving Impaired Ca Handling and Arrhythmogenesis.异常的 PLN-R14del 蛋白相互作用加剧 SERCA2a 抑制，导致钙处理和心律失常发生受损。
Int J Mol Sci. 2022 Jun 22;23(13):6947. doi: 10.3390/ijms23136947.
6
MicroRNAs and Calcium Signaling in Heart Disease.微小 RNA 与心脏疾病中的钙信号转导
Int J Mol Sci. 2021 Sep 30;22(19):10582. doi: 10.3390/ijms221910582.
7
FAM20C Overview: Classic and Novel Targets, Pathogenic Variants and Raine Syndrome Phenotypes.FAM20C 概述：经典和新型靶标、致病性变异和 Raine 综合征表型。
Int J Mol Sci. 2021 Jul 27;22(15):8039. doi: 10.3390/ijms22158039.
8
Role of induced pluripotent stem cells in diagnostic cardiology.诱导多能干细胞在诊断心脏病学中的作用。
World J Stem Cells. 2021 May 26;13(5):331-341. doi: 10.4252/wjsc.v13.i5.331.
9
Sarcoplasmic reticulum calcium mishandling: central tenet in heart failure?肌浆网钙处理异常：心力衰竭的核心原则？
Biophys Rev. 2020 Aug;12(4):865-878. doi: 10.1007/s12551-020-00736-y. Epub 2020 Jul 22.
10
Thinking outside of the cell: Secreted protein kinases in bacteria, parasites, and mammals.超越细胞思维：细菌、寄生虫和哺乳动物中的分泌蛋白激酶。
IUBMB Life. 2019 Jun;71(6):749-759. doi: 10.1002/iub.2040. Epub 2019 Apr 2.
富含组氨酸的钙结合蛋白：肌浆网钙螯合及心脏功能的调节因子。
J Mol Cell Cardiol. 2006 May;40(5):653-65. doi: 10.1016/j.yjmcc.2006.02.003.
4
Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure.胺碘酮或植入式心脏复律除颤器用于治疗充血性心力衰竭。
N Engl J Med. 2005 Jan 20;352(3):225-37. doi: 10.1056/NEJMoa043399.
5
Regulation of myocardial function by histidine-rich, calcium-binding protein.富含组氨酸的钙结合蛋白对心肌功能的调节
Am J Physiol Heart Circ Physiol. 2004 Oct;287(4):H1705-11. doi: 10.1152/ajpheart.01211.2003. Epub 2004 Jun 10.
6
Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence.根据氨基酸序列预测蛋白质的翻译后糖基化和磷酸化。
Proteomics. 2004 Jun;4(6):1633-49. doi: 10.1002/pmic.200300771.
7
Cellular basis of triggered arrhythmias in heart failure.心力衰竭中触发心律失常的细胞基础。
Trends Cardiovasc Med. 2004 Feb;14(2):61-6. doi: 10.1016/j.tcm.2003.12.002.
8
Electrophysiological changes in heart failure and their relationship to arrhythmogenesis.心力衰竭时的电生理变化及其与心律失常发生的关系。
Cardiovasc Res. 2004 Feb 1;61(2):208-17. doi: 10.1016/j.cardiores.2003.11.018.
9
Noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy: results of the Marburg Cardiomyopathy Study.特发性扩张型心肌病的无创性心律失常风险分层：马尔堡心肌病研究结果
Circulation. 2003 Dec 9;108(23):2883-91. doi: 10.1161/01.CIR.0000100721.52503.85. Epub 2003 Nov 17.
10
A missense mutation in the CASQ2 gene is associated with autosomal-recessive catecholamine-induced polymorphic ventricular tachycardia.CASQ2基因中的错义突变与常染色体隐性遗传性儿茶酚胺诱导的多形性室性心动过速相关。
Trends Cardiovasc Med. 2003 May;13(4):148-51. doi: 10.1016/s1050-1738(03)00025-2.