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. 2016 Feb 12:16:31.
doi: 10.1186/s12890-016-0192-6.

Analysis of mitochondrial DNA alteration in new phenotype ACOS

G E Carpagnano  1 , D Lacedonia  2 , M Malerba  3 , G A Palmiotti  4 , G Cotugno  5 , M Carone  6 , M P Foschino-Barbaro  7
Affiliations

Analysis of mitochondrial DNA alteration in new phenotype ACOS

G E Carpagnano et al. BMC Pulm Med. .

Abstract

Background: Mitochondria contain their own DNA (MtDNA) that is very sensitive to oxidative stress and as a consequence could be damaged in quantity. Oxidative stress is largely recognized to play a key role in the pathogenesis of asthma and COPD and might have a role in the new intermediate phenotype ACOS (asthma-COPD overlap syndrome). The aim of this study was to investigate MtDNA alterations, as an expression of mitochondrial dysfunction, in ACOS and to verify whether they might help in the identification of this new phenotype and in its differentiation from asthma and COPD.

Methods: Ten (10) ACOS according to Spanish guidelines, 13 ACOS according to GINA guidelines, 13 COPD, 14 asthmatic patients and ten normal subjects were enrolled. They further underwent a blood, induced sputum and exhaled nitric oxide collection. Content of MtDNA and nuclear DNA (nDNA) were measured in the blood cells of patients by Real Time PCR.

Results: ACOS patients showed an increase of MtDNA/nDNA ratio. Dividing ACOS according to guidelines, those from the Spanish showed a higher value of MtDNA/nDNA compared to those from GINA/GOLD (92.69 ± 7.31 vs 80.68 ± 4.16). Spanish ACOS presented MtDNA/nDNA ratio closer to COPD than asthma. MtDNA was higher in asthmatic, COPD, GINA and Spanish ACOS patients compared to healthy subjects (73.30 ± 4.47-137.0 ± 19.45-80.68 ± 4.16-92.69 ± 7.31 vs 65.97 ± 20.56).

Conclusion: We found an increase of MtDNA/nDNA ratio in ACOS subjects that led us to conclude that there is presence of mitochondrial dysfunction in this disease, that makes it closer to COPD than to asthma. Although the MtDNA/nDNA ratio results are a useful marker for differential diagnosis from asthma, COPD and ACOS, further studies are needed to confirm the potentiality of MtDNA/nDNA ratio and to a better characterization of ACOS.

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Figures

Fig. 1
Fig. 1
Differences between ratio Mitochondrial/nuclear DNA in ACOS according to Spanish or GINA guidelines, asthmatic and COPD patients. MtDNA/nDNA was higher in all the groups suggesting the presence of inflammation; ACOS patients present an intermediate value of MtDNA/nDNA with respect to Asthma and COPD
Fig. 2
Fig. 2
Kinetic curves of MtDNA obtained by q-Real Time PCR in whole blood from ACOS GINA patients. The reported signal (Rn) is calculated by dividing the amount of florescence emitted by the reporter by the amount of fluorescence emitted by a passive report (log ΔRn). Fluorescence is plotted vs cycle number
Fig. 3
Fig. 3
Comparison of the absolute MtDNA copy number of different groups. The values are represented with arithmetic mean and standard deviation
Fig. 4
Fig. 4
Positive correlation between ratio Mitochondrial/nuclear DNA and pack years. Cigarette smoking is associated with increased inflammation. This is further demonstrated by the increase of MtDNA/nDNA
Fig. 5
Fig. 5
Positive correlation between ratio Mitochondrial/nuclear DNA and neutrophils percentage in the induced sputum. The presence of neutrophils in the sputum is associated with a higher grade of inflammation
See this image and copyright information in PMC

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