Leukocyte Mitochondrial DNA Copy Number Is Associated with Chronic Obstructive Pulmonary Disease.

Shih-Feng Liu,Meng-Chih Lin,Yung-Che Chen,Ho-Chang Kuo,Chia-Cheng Tseng,Ching-Wan Tseng,Hung-Tu Huang,Yunchao Su

doi:10.1371/journal.pone.0138716

Abstract

BackgroundOxidative stress is known to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Evidence suggests that leukocytes mitochondria DNA (mtDNA) is susceptible to undergo mutations, insertions, or depletion in response to reactive oxidative stress (ROS). We hypothesize that mtDNA copy number is associated with the development of COPD.Methodology/Principal FindingsRelative mtDNA copy number was measured by a quantitative real-time PCR assay using DNA extracted from peripheral leukocytes. MtDNA copy number of peripheral leukocytes in the COPD group (n = 86) is significantly decreased compared with non-smoker group (n = 77) (250.3± 21.5 VS. 464.2± 49.9, P<0.001). MtDNA copy number in the COPD group was less than that in the healthy smoking group, but P value nearly achieved significance (250.3± 21.5 VS. 404.0± 76.7, P = 0.08) MtDNA copy number has no significance with age, gender, body mass index, current smoking, and pack-years in COPD group, healthy smoker group and no smoker group, respectively. Serum glutathione level in the COPD group is significantly decreased compared with healthy smoker and non-smoker groups (4.5± 1.3 VS. 6.2± 1.9 and 4.5± 1.3 VS. 7.1±1.1 mU/mL; P<0.001 respectively). Pearson correlation test shows a significant liner correlation between mtDNA copy number and serum glutathione level (R = 0.2, P = 0.009).Conclusions/SignificanceCOPD is associated with decreased leukocyte mtDNA copy number and serum glutathione. COPD is a regulatory disorder of leukocytes mitochondria. However, further studies are needed to determine the real mechanisms about the gene and the function of mitochondria.

Highlights

Chronic obstructive pulmonary disease (COPD) is a slowly progressive condition characterized by poorly reversible airflow limitation that is usually progressive and associated with an abnormal inflammatory response of the lung
COPD is associated with decreased leukocyte mitochondria DNA (mtDNA) copy number and serum glutathione
COPD is a regulatory disorder of leukocytes mitochondria

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a slowly progressive condition characterized by poorly reversible airflow limitation that is usually progressive and associated with an abnormal inflammatory response of the lung. Increasing evidence suggests oxidative stress and inflammation in the lungs may be responsible for many of the systemic effects of COPD [4]. Peripheral blood leukocytes in COPD patients have been shown to release more ROS than in normal subjects, which may contribute to morbidity and mortality [7]. Oxidative stress is known to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Evidence suggests that leukocytes mitochondria DNA (mtDNA) is susceptible to undergo mutations, insertions, or depletion in response to reactive oxidative stress (ROS). We hypothesize that mtDNA copy number is associated with the development of COPD

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Discussion

Conclusion