扩张型心肌病和系统性免疫相关疾病患者的基因状况

IF 10.3 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC. Heart failure Pub Date : 2025-01-01 DOI:10.1016/j.jchf.2024.08.011

Sophie L.V.M. Stroeks MD , Michiel T.H.M. Henkens MD, PhD , Fernando Dominguez MD, PhD , Marco Merlo MD , Debby M.E.I. Hellebrekers PhD , Esther Gonzalez-Lopez MD, PhD , Matteo dal Ferro MD , Juan Pablo Ochoa MD, PhD , Francesco Venturelli MD , Godelieve R.F. Claes PhD , Max F.G.H.M. Venner MD , Ingrid P.C. Krapels MD, PhD , Els K. Vanhoutte MD, PhD , Pieter van Paassen MD, PhD , Arthur van den Wijngaard PhD , Maurits A. Sikking MD , Rick van Leeuwen BSc , Myrurgia Abdul Hamid MD , Xiaofei Li MD, PhD , Han G. Brunner MD, PhD , Job A.J. Verdonschot MD, PhD

{"title":"扩张型心肌病和系统性免疫相关疾病患者的基因状况","authors":"Sophie L.V.M. Stroeks MD , Michiel T.H.M. Henkens MD, PhD , Fernando Dominguez MD, PhD , Marco Merlo MD , Debby M.E.I. Hellebrekers PhD , Esther Gonzalez-Lopez MD, PhD , Matteo dal Ferro MD , Juan Pablo Ochoa MD, PhD , Francesco Venturelli MD , Godelieve R.F. Claes PhD , Max F.G.H.M. Venner MD , Ingrid P.C. Krapels MD, PhD , Els K. Vanhoutte MD, PhD , Pieter van Paassen MD, PhD , Arthur van den Wijngaard PhD , Maurits A. Sikking MD , Rick van Leeuwen BSc , Myrurgia Abdul Hamid MD , Xiaofei Li MD, PhD , Han G. Brunner MD, PhD , Job A.J. Verdonschot MD, PhD","doi":"10.1016/j.jchf.2024.08.011","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Systemic immune-mediated diseases (SIDs) are a well-known cause of dilated cardiomyopathy (DCM), a cardiac phenotype influenced by genetic predispositions and environmental factors.</div></div><div><h3>Objectives</h3><div>This study sought to examine if an underlying genetic predisposition is present in patients with DCM and SID.</div></div><div><h3>Methods</h3><div>Genotyped DCM-SID patients (n = 183) were enrolled at 3 European centers. Genetic variants were compared with healthy control subjects (n = 20,917), DCM patients without SID (n = 560), and individuals with a suspicion of an SID (n = 1,333). Clinical outcomes included all-cause mortality, heart failure hospitalization, and life-threatening arrhythmias.</div></div><div><h3>Results</h3><div>The SID diagnosis preceded the DCM diagnosis by 4.8 months (Q1-Q3: −68.4 to +2.4 months). The prevalence of pathogenic/likely pathogenic (P/LP) variants in DCM patients with an SID from the Maastricht cohort was 17.1%, compared with 1.9% in healthy control subjects (<em>P <</em> 0.001). In the Madrid/Trieste cohort, the prevalence was 20.5% (<em>P <</em> 0.001). Truncating variants showed the strongest enrichment (10.7% [OR: 24.5] (Maastricht) and 16% [OR: 116.6 (Madrid/Trieste); both <em>P <</em> 0.001), with truncating <em>TTN</em> (titin) variant (TTNtv) being the most prevalent. Left ventricular ejection fraction at presentation was reduced in TTNtv-SID patients compared with DCM patients with SID without a P/LP (<em>P =</em> 0.016). The presence of a P/LP variant in DCM-SID had no impact on clinical outcomes over a median follow-up of 8.4 years (Q1-Q3: 4.9-12.1 years).</div></div><div><h3>Conclusions</h3><div>One in 6 DCM patients with an SID has an underlying P/LP variant in a DCM-associated gene. This highlights the role of genetic testing in those patients with immune-mediated DCM, and supports the concept that autoimmunity may play a role in unveiling a DCM phenotype in genotype-positive individuals.</div></div>","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":"13 1","pages":"Pages 133-145"},"PeriodicalIF":10.3000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genetic Landscape of Patients With Dilated Cardiomyopathy and a Systemic Immune-Mediated Disease\",\"authors\":\"Sophie L.V.M. Stroeks MD , Michiel T.H.M. Henkens MD, PhD , Fernando Dominguez MD, PhD , Marco Merlo MD , Debby M.E.I. Hellebrekers PhD , Esther Gonzalez-Lopez MD, PhD , Matteo dal Ferro MD , Juan Pablo Ochoa MD, PhD , Francesco Venturelli MD , Godelieve R.F. Claes PhD , Max F.G.H.M. Venner MD , Ingrid P.C. Krapels MD, PhD , Els K. Vanhoutte MD, PhD , Pieter van Paassen MD, PhD , Arthur van den Wijngaard PhD , Maurits A. Sikking MD , Rick van Leeuwen BSc , Myrurgia Abdul Hamid MD , Xiaofei Li MD, PhD , Han G. Brunner MD, PhD , Job A.J. Verdonschot MD, PhD\",\"doi\":\"10.1016/j.jchf.2024.08.011\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Systemic immune-mediated diseases (SIDs) are a well-known cause of dilated cardiomyopathy (DCM), a cardiac phenotype influenced by genetic predispositions and environmental factors.</div></div><div><h3>Objectives</h3><div>This study sought to examine if an underlying genetic predisposition is present in patients with DCM and SID.</div></div><div><h3>Methods</h3><div>Genotyped DCM-SID patients (n = 183) were enrolled at 3 European centers. Genetic variants were compared with healthy control subjects (n = 20,917), DCM patients without SID (n = 560), and individuals with a suspicion of an SID (n = 1,333). Clinical outcomes included all-cause mortality, heart failure hospitalization, and life-threatening arrhythmias.</div></div><div><h3>Results</h3><div>The SID diagnosis preceded the DCM diagnosis by 4.8 months (Q1-Q3: −68.4 to +2.4 months). The prevalence of pathogenic/likely pathogenic (P/LP) variants in DCM patients with an SID from the Maastricht cohort was 17.1%, compared with 1.9% in healthy control subjects (<em>P <</em> 0.001). In the Madrid/Trieste cohort, the prevalence was 20.5% (<em>P <</em> 0.001). Truncating variants showed the strongest enrichment (10.7% [OR: 24.5] (Maastricht) and 16% [OR: 116.6 (Madrid/Trieste); both <em>P <</em> 0.001), with truncating <em>TTN</em> (titin) variant (TTNtv) being the most prevalent. Left ventricular ejection fraction at presentation was reduced in TTNtv-SID patients compared with DCM patients with SID without a P/LP (<em>P =</em> 0.016). The presence of a P/LP variant in DCM-SID had no impact on clinical outcomes over a median follow-up of 8.4 years (Q1-Q3: 4.9-12.1 years).</div></div><div><h3>Conclusions</h3><div>One in 6 DCM patients with an SID has an underlying P/LP variant in a DCM-associated gene. This highlights the role of genetic testing in those patients with immune-mediated DCM, and supports the concept that autoimmunity may play a role in unveiling a DCM phenotype in genotype-positive individuals.</div></div>\",\"PeriodicalId\":14687,\"journal\":{\"name\":\"JACC. Heart failure\",\"volume\":\"13 1\",\"pages\":\"Pages 133-145\"},\"PeriodicalIF\":10.3000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JACC. Heart failure\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2213177924006176\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JACC. Heart failure","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2213177924006176","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}

引用次数: 0

摘要

背景：众所周知，全身性免疫介导疾病（SID）是扩张型心肌病（DCM）的病因，而扩张型心肌病是一种受遗传倾向和环境因素影响的心脏表型：本研究旨在探讨 DCM 和 SID 患者是否存在潜在的遗传易感性：方法：欧洲 3 个中心招募了基因分型的 DCM-SID 患者（n = 183）。遗传变异与健康对照受试者（n = 20,917）、无 SID 的 DCM 患者（n = 560）和怀疑有 SID 的个体（n = 1,333）进行了比较。临床结果包括全因死亡率、心衰住院率和危及生命的心律失常：结果：SID诊断比DCM诊断早4.8个月（Q1-Q3：-68.4至+2.4个月）。在马斯特里赫特队列中，患有 SID 的 DCM 患者中致病性/可能致病性（P/LP）变异的发生率为 17.1%，而在健康对照组中为 1.9%（P < 0.001）。在马德里/特里亚斯特队列中，发病率为 20.5%（P < 0.001）。截短变异表现出最强的富集性（10.7% [OR: 24.5]（马斯特里赫特）和 16% [OR: 116.6（马德里/特里亚斯特）；P 均<0.001），其中截短 TTN（钛蛋白）变异（TTNtv）最为普遍。与不存在 P/LP 的 SID DCM 患者相比，TTNtv-SID 患者发病时的左心室射血分数降低（P = 0.016）。在中位随访8.4年（Q1-Q3：4.9-12.1年）期间，DCM-SID患者出现P/LP变异对临床结果没有影响：结论：每 6 名患有 SID 的 DCM 患者中，就有一人的 DCM 相关基因存在潜在的 P/LP 变异。这凸显了基因检测在免疫介导的 DCM 患者中的作用，并支持了自身免疫可能在基因型阳性个体中揭示 DCM 表型的概念。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Genetic Landscape of Patients With Dilated Cardiomyopathy and a Systemic Immune-Mediated Disease

Background

Systemic immune-mediated diseases (SIDs) are a well-known cause of dilated cardiomyopathy (DCM), a cardiac phenotype influenced by genetic predispositions and environmental factors.

Objectives

This study sought to examine if an underlying genetic predisposition is present in patients with DCM and SID.

Methods

Genotyped DCM-SID patients (n = 183) were enrolled at 3 European centers. Genetic variants were compared with healthy control subjects (n = 20,917), DCM patients without SID (n = 560), and individuals with a suspicion of an SID (n = 1,333). Clinical outcomes included all-cause mortality, heart failure hospitalization, and life-threatening arrhythmias.

Results

The SID diagnosis preceded the DCM diagnosis by 4.8 months (Q1-Q3: −68.4 to +2.4 months). The prevalence of pathogenic/likely pathogenic (P/LP) variants in DCM patients with an SID from the Maastricht cohort was 17.1%, compared with 1.9% in healthy control subjects (P < 0.001). In the Madrid/Trieste cohort, the prevalence was 20.5% (P < 0.001). Truncating variants showed the strongest enrichment (10.7% [OR: 24.5] (Maastricht) and 16% [OR: 116.6 (Madrid/Trieste); both P < 0.001), with truncating TTN (titin) variant (TTNtv) being the most prevalent. Left ventricular ejection fraction at presentation was reduced in TTNtv-SID patients compared with DCM patients with SID without a P/LP (P = 0.016). The presence of a P/LP variant in DCM-SID had no impact on clinical outcomes over a median follow-up of 8.4 years (Q1-Q3: 4.9-12.1 years).

Conclusions

One in 6 DCM patients with an SID has an underlying P/LP variant in a DCM-associated gene. This highlights the role of genetic testing in those patients with immune-mediated DCM, and supports the concept that autoimmunity may play a role in unveiling a DCM phenotype in genotype-positive individuals.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

JACC. Heart failure CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

21.20

自引率

2.30%

发文量

164

期刊介绍： JACC: Heart Failure publishes crucial findings on the pathophysiology, diagnosis, treatment, and care of heart failure patients. The goal is to enhance understanding through timely scientific communication on disease, clinical trials, outcomes, and therapeutic advances. The Journal fosters interdisciplinary connections with neuroscience, pulmonary medicine, nephrology, electrophysiology, and surgery related to heart failure. It also covers articles on pharmacogenetics, biomarkers, and metabolomics.