Quantitative expression of the mutated lamin A/C gene in patients with cardiolaminopathy
Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved..
OBJECTIVES: The authors sought to investigate the gene and protein expression in Lamin A/C (LMNA)-mutated dilated cardiolaminopathy (DCM) patients (DCM(LMNAMut)) versus LMNA-wild-type DCM (DCM(LMNAWT)), and normal controls (CTRL(LMNAWT)).
BACKGROUND: Dilated cardiolaminopathies are clinically characterized by high arrhythmogenic risk and caused by LMNA mutations. Little is known regarding quantitative gene expression (QGE) of the LMNA gene in blood and myocardium, as well as regarding myocardial expression of the lamin A/C protein.
METHODS: Using the comparative ΔΔCT method, we evaluated the QGE of LMNA (QGE(LMNA)) in peripheral blood and myocardial RNA from carriers of LMNA mutations, versus blood and myocardial samples from DCM(LMNAWT) patients and CTRL(LMNAWT) individuals. After generating reference values in normal controls, QGE(LMNA) was performed in 311 consecutive patients and relatives, blind to genotype, to assess the predictive value of QGE(LMNA) for the identification of mutation carriers. In parallel, Lamin A/C was investigated in myocardial samples from DCM(LMNAMut) versus DCM(LMNAWT) versus normal hearts (CTRL(LMNAWT)).
RESULTS: LMNA was significantly underexpressed in mRNA from peripheral blood and myocardium of DCM(LMNAMut) patients versus DCM(LMNAWT) and CTRL(LMNAWT). In 311 individuals, blind to genotype, the QGE(LMNA) showed 100% sensitivity and 87% specificity as a predictor of LMNA mutations. The receiver-operating characteristic curve analysis yielded an area under the curve of 0.957 (p < 0.001). Loss of protein in cardiomyocytes' nuclei was documented in DCM(LMNAMut) patients.
CONCLUSIONS: The reduced expression of LMNA gene in blood is a novel potential predictive biomarker for dilated cardiolaminopathies with parallel loss of protein expression in cardiomyocyte nuclei.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2012 |
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| Erschienen: |
2012 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:60 |
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| Enthalten in: |
Journal of the American College of Cardiology - 60(2012), 19 vom: 06. Nov., Seite 1916-20 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Narula, Nupoor [VerfasserIn] |
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| Links: |
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| Themen: |
Biomarkers |
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| Anmerkungen: |
Date Completed 09.01.2013 Date Revised 19.11.2015 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jacc.2012.05.059 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM221793127 |
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| 100 | 1 | |a Narula, Nupoor |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Quantitative expression of the mutated lamin A/C gene in patients with cardiolaminopathy |
| 264 | 1 | |c 2012 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 09.01.2013 | ||
| 500 | |a Date Revised 19.11.2015 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a OBJECTIVES: The authors sought to investigate the gene and protein expression in Lamin A/C (LMNA)-mutated dilated cardiolaminopathy (DCM) patients (DCM(LMNAMut)) versus LMNA-wild-type DCM (DCM(LMNAWT)), and normal controls (CTRL(LMNAWT)) | ||
| 520 | |a BACKGROUND: Dilated cardiolaminopathies are clinically characterized by high arrhythmogenic risk and caused by LMNA mutations. Little is known regarding quantitative gene expression (QGE) of the LMNA gene in blood and myocardium, as well as regarding myocardial expression of the lamin A/C protein | ||
| 520 | |a METHODS: Using the comparative ΔΔCT method, we evaluated the QGE of LMNA (QGE(LMNA)) in peripheral blood and myocardial RNA from carriers of LMNA mutations, versus blood and myocardial samples from DCM(LMNAWT) patients and CTRL(LMNAWT) individuals. After generating reference values in normal controls, QGE(LMNA) was performed in 311 consecutive patients and relatives, blind to genotype, to assess the predictive value of QGE(LMNA) for the identification of mutation carriers. In parallel, Lamin A/C was investigated in myocardial samples from DCM(LMNAMut) versus DCM(LMNAWT) versus normal hearts (CTRL(LMNAWT)) | ||
| 520 | |a RESULTS: LMNA was significantly underexpressed in mRNA from peripheral blood and myocardium of DCM(LMNAMut) patients versus DCM(LMNAWT) and CTRL(LMNAWT). In 311 individuals, blind to genotype, the QGE(LMNA) showed 100% sensitivity and 87% specificity as a predictor of LMNA mutations. The receiver-operating characteristic curve analysis yielded an area under the curve of 0.957 (p < 0.001). Loss of protein in cardiomyocytes' nuclei was documented in DCM(LMNAMut) patients | ||
| 520 | |a CONCLUSIONS: The reduced expression of LMNA gene in blood is a novel potential predictive biomarker for dilated cardiolaminopathies with parallel loss of protein expression in cardiomyocyte nuclei | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a LMNA protein, human |2 NLM | |
| 650 | 7 | |a Lamin Type A |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 700 | 1 | |a Favalli, Valentina |e verfasserin |4 aut | |
| 700 | 1 | |a Tarantino, Paolo |e verfasserin |4 aut | |
| 700 | 1 | |a Grasso, Maurizia |e verfasserin |4 aut | |
| 700 | 1 | |a Pilotto, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Bellazzi, Riccardo |e verfasserin |4 aut | |
| 700 | 1 | |a Serio, Alessandra |e verfasserin |4 aut | |
| 700 | 1 | |a Gambarin, Fabiana I |e verfasserin |4 aut | |
| 700 | 1 | |a Charron, Philippe |e verfasserin |4 aut | |
| 700 | 1 | |a Meder, Benjamin |e verfasserin |4 aut | |
| 700 | 1 | |a Pinto, Yigal |e verfasserin |4 aut | |
| 700 | 1 | |a Elliott, Perry M |e verfasserin |4 aut | |
| 700 | 1 | |a Mogensen, Jens |e verfasserin |4 aut | |
| 700 | 1 | |a Bolognesi, Martino |e verfasserin |4 aut | |
| 700 | 1 | |a Bollati, Michela |e verfasserin |4 aut | |
| 700 | 1 | |a Arbustini, Eloisa |e verfasserin |4 aut | |
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