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Tissue-Specific Ultra-Short Telomeres in Chronic Obstructive Pulmonary Disease

PURPOSE: Telomere biology, especially tissue-specific ultra-short telomeres, might provide a strong contribution to our current knowledge in COPD development as well as a predictive marker for prognosis. To test this hypothesis, we investigated telomere lengths in lung tissue and leukocytes in patie...

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Autores principales: Cagsin, Huseyin, Uzan, Ali, Tosun, Ozgur, Rasmussen, Finn, Serakinci, Nedime
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608580/
https://www.ncbi.nlm.nih.gov/pubmed/33154635
http://dx.doi.org/10.2147/COPD.S267799
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author Cagsin, Huseyin
Uzan, Ali
Tosun, Ozgur
Rasmussen, Finn
Serakinci, Nedime
author_facet Cagsin, Huseyin
Uzan, Ali
Tosun, Ozgur
Rasmussen, Finn
Serakinci, Nedime
author_sort Cagsin, Huseyin
collection PubMed
description PURPOSE: Telomere biology, especially tissue-specific ultra-short telomeres, might provide a strong contribution to our current knowledge in COPD development as well as a predictive marker for prognosis. To test this hypothesis, we investigated telomere lengths in lung tissue and leukocytes in patients diagnosed with COPD. PATIENTS AND METHODS: Thirty-two patients were included in the current study. All patients showed a post-bronchodilator ratio of less than 70% post-bronchodilator predicted value of forced expiratory volume in second (FEV1%), mean 56%; range [19% to 86%]. To be able to investigate ultra-short telomeres, universal single telomere length analysis (U-STELA) was used. RESULTS: Our results showed a higher level of the ultra-short telomere presence in bronchoalveolar lavage (BAL) cells when compared to leukocytes with statistical significance t(62)=5.771, p<0.00001. The FEV1% was lower in subjects with ultra-short telomeres in BAL (50.6% vs 81.6%: p<0.001) and in ultra-short telomeres in blood leukocytes (37.3% vs 58.5%: p=0.051) when compared to subjects without ultra-short telomeres in leukocytes. Furthermore, the patients who had ultra-short telomeres in BAL samples were significantly older (p=0.014) than patients who did not have ultra-short telomeres. Ultra-short telomeres in BAL (p=0.05) but not in leukocytes (p=0.33) were associated with FEV1% in a regressions model adjusting for age (p<0.0001), ever smoking (p<0.0001) and sex (p=0.71). The patients with ultra-short telomeres were graded higher in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification (p=0.006). CONCLUSION: This study emphasizes the need to investigate the correct tissue to get a representative evaluation of the stage or advancedness of COPD. To our knowledge, this is the first study to show that there is a correlation between the presence of ultra-short telomeres in lung tissue and COPD severity. Our results suggest that ultra-short telomeres are involved in the molecular pathogenesis of COPD and might be used as a tissue-specific predictive biomarker.
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spelling pubmed-76085802020-11-04 Tissue-Specific Ultra-Short Telomeres in Chronic Obstructive Pulmonary Disease Cagsin, Huseyin Uzan, Ali Tosun, Ozgur Rasmussen, Finn Serakinci, Nedime Int J Chron Obstruct Pulmon Dis Original Research PURPOSE: Telomere biology, especially tissue-specific ultra-short telomeres, might provide a strong contribution to our current knowledge in COPD development as well as a predictive marker for prognosis. To test this hypothesis, we investigated telomere lengths in lung tissue and leukocytes in patients diagnosed with COPD. PATIENTS AND METHODS: Thirty-two patients were included in the current study. All patients showed a post-bronchodilator ratio of less than 70% post-bronchodilator predicted value of forced expiratory volume in second (FEV1%), mean 56%; range [19% to 86%]. To be able to investigate ultra-short telomeres, universal single telomere length analysis (U-STELA) was used. RESULTS: Our results showed a higher level of the ultra-short telomere presence in bronchoalveolar lavage (BAL) cells when compared to leukocytes with statistical significance t(62)=5.771, p<0.00001. The FEV1% was lower in subjects with ultra-short telomeres in BAL (50.6% vs 81.6%: p<0.001) and in ultra-short telomeres in blood leukocytes (37.3% vs 58.5%: p=0.051) when compared to subjects without ultra-short telomeres in leukocytes. Furthermore, the patients who had ultra-short telomeres in BAL samples were significantly older (p=0.014) than patients who did not have ultra-short telomeres. Ultra-short telomeres in BAL (p=0.05) but not in leukocytes (p=0.33) were associated with FEV1% in a regressions model adjusting for age (p<0.0001), ever smoking (p<0.0001) and sex (p=0.71). The patients with ultra-short telomeres were graded higher in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification (p=0.006). CONCLUSION: This study emphasizes the need to investigate the correct tissue to get a representative evaluation of the stage or advancedness of COPD. To our knowledge, this is the first study to show that there is a correlation between the presence of ultra-short telomeres in lung tissue and COPD severity. Our results suggest that ultra-short telomeres are involved in the molecular pathogenesis of COPD and might be used as a tissue-specific predictive biomarker. Dove 2020-10-30 /pmc/articles/PMC7608580/ /pubmed/33154635 http://dx.doi.org/10.2147/COPD.S267799 Text en © 2020 Cagsin et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Cagsin, Huseyin
Uzan, Ali
Tosun, Ozgur
Rasmussen, Finn
Serakinci, Nedime
Tissue-Specific Ultra-Short Telomeres in Chronic Obstructive Pulmonary Disease
title Tissue-Specific Ultra-Short Telomeres in Chronic Obstructive Pulmonary Disease
title_full Tissue-Specific Ultra-Short Telomeres in Chronic Obstructive Pulmonary Disease
title_fullStr Tissue-Specific Ultra-Short Telomeres in Chronic Obstructive Pulmonary Disease
title_full_unstemmed Tissue-Specific Ultra-Short Telomeres in Chronic Obstructive Pulmonary Disease
title_short Tissue-Specific Ultra-Short Telomeres in Chronic Obstructive Pulmonary Disease
title_sort tissue-specific ultra-short telomeres in chronic obstructive pulmonary disease
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608580/
https://www.ncbi.nlm.nih.gov/pubmed/33154635
http://dx.doi.org/10.2147/COPD.S267799
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