Analysis of mitochondrial DNA alteration in new phenotype ACOS.
Analysis of mitochondrial DNA alteration in new phenotype ACOS.
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DOI：
10.1186/s12890-016-0192-6
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发表时间：
2016-02-12
影响因子：
3.1
通讯作者：
Foschino-Barbaro MP
中科院分区：
文献类型：
--
作者：
Carpagnano GE;Lacedonia D;Malerba M;Palmiotti GA;Cotugno G;Carone M;Foschino-Barbaro MP
线粒体含有它们自己的DNA（MtDNA），其对氧化应激非常敏感，因此可能在数量上受到损伤。氧化应激在哮喘和COPD的发病机制中起关键作用，并可能在新的中间表型ACOS（哮喘-COPD重叠综合征）中起作用。本研究的目的是调查线粒体DNA的改变，作为线粒体功能障碍的表达，在ACOS和验证他们是否可能有助于识别这种新的表型，并在其从哮喘和COPD的分化。根据西班牙指南入组了10例ACOS，根据GINA指南入组了13例ACOS，13例COPD患者，14例哮喘患者和10例正常受试者。他们进一步进行了血液，诱导痰和呼出的一氧化氮收集。采用真实的时间PCR法检测患者血细胞线粒体DNA和核DNA含量。ACOS患者MtDNA/nDNA比值升高。根据指南对ACOS进行分类，西班牙人的MtDNA/nDNA值高于GINA/GOLD（92.69 ± 7.31 vs 80.68 ± 4.16）。与哮喘相比，西班牙ACOS的MtDNA/nDNA比值更接近COPD。与健康受试者相比，哮喘、COPD、GINA和西班牙ACOS患者的MtDNA较高（73.30 ± 4.47-137.0 ± 19.45-80.68 ± 4.16-92.69 ± 7.31 vs 65.97 ± 20.56）。我们发现ACOS受试者中MtDNA/nDNA比率增加，这使我们得出结论，在这种疾病中存在线粒体功能障碍，这使其更接近COPD而不是哮喘。虽然MtDNA/nDNA比值结果是鉴别哮喘、COPD和ACOS的有用标志物，但需要进一步研究来证实MtDNA/nDNA比值的潜力，并更好地表征ACOS。本文的在线版本（doi：10.1186/s12890-016-0192-6）包含补充材料，可供授权用户使用。
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. 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. 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). 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. The online version of this article (doi:10.1186/s12890-016-0192-6) contains supplementary material, which is available to authorized users.