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Published online before print May 28, 2008
Eur Respir J 2008, doi:10.1183/09031936.00169307
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ORIGINAL ARTICLE

Microsatellite DNA Instability and Chronic Obstructive Pulmonary Disease Exacerbations

D. Makris 1, N. Tzanakis 1, A. Damianaki 2, E. Ntaoukakis 2, E. Neofytou 1, M. Zervou 1, N.M. Siafakas 1*, E.G. Tzortzaki 1

1 Dept of Thoracic Medicine, University Hospital, Medical School, University of Crete, Heraklion, Greece
2 Dept of Pulmonology, Agios Georgios General Hospital, Chania, Crete, Greece

* To whom correspondence should be addressed. E-mail: siafak{at}med.uoc.gr.


  Abstract

Increased frequency of Microsatellite DNA Instability(MSI) has been detected in sputum of COPD patients. Our aim was to investigate the relationship between MSI in sputum cells and exacerbation frequency which is an important parameter in the clinical course of the disease.

Induced sputum samples and peripheral blood obtained from 36 patients with COPD at stable state were analyzed. The control group consisted of 30 non-smokers healthy subjects. DNA was extracted and analyzed for MSI using the following Microsatellite markers: RH70958, D5S207, D6S2223, D6S344, D6S263, G29802, D13S71, D14S588, D14S292, D17S250. Following MSI analysis, exacerbations were recorded for three years in total.

No MSI was detected in healthy non-smokers. Eighteen(18) out of thirty six(36) patients (50%) exhibited MSI in their sputum cells (p<0.0001). Patients exhibited MSI showed significantly increased frequency of exacerbations compared to patients that did not (p=0.003). In addition, a significant increased frequency of purulent (p=0.002) and of severe type exacerbations (p=0.001) was found in patients exhibiting MSI. Patients positive for marker G29802 or D13S71 or D14S588 presented increased exacerbation frequency (p<0.01).

The significant association between MSI and COPD exacerbations indicates that somatic mutations could be involved in the pathogenesis and natural history of the disease.

Keywords:  Chronic bronchitis, emphysema, microsatellite DNA, smoking, somatic mutation, sputum




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