International Journal of COPD (Oct 2020)
Tissue-Specific Ultra-Short Telomeres in Chronic Obstructive Pulmonary Disease
Abstract
Huseyin Cagsin,1,2 Ali Uzan,3 Ozgur Tosun,4 Finn Rasmussen,3,5 Nedime Serakinci1,2 1Department of Medical Genetics, Faculty of Medicine, Near East University, Nicosia, Cyprus; 2Department of Molecular Biology of Genetics, Arts and Sciences Faculty, Near East University, Nicosia, Cyprus; 3Department of Allergy Sleep and Respiratory Medicine, Near East University Hospital, Nicosia, Cyprus; 4Department of Biostatistics, Faculty of Medicine, Near East University, Nicosia, Cyprus; 5Section of Respiratory Medicine; Department of Internal Medicine, Sydvestjysk Hospital, Esbjerg, DenmarkCorrespondence: Nedime SerakinciNear East University, Faculty of Medicine, Department of Medical Genetics, Nicosia 999058, North Cyprus Tel +90 392 675 1000 Ext 3017Email [email protected]: 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.Keywords: COPD, ultra-short telomeres, BAL, tissue-specific
