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Aging and disease    2016, Vol. 7 Issue (5) : 604-613     DOI: 10.14336/AD.2016.0215
Original Article |
Oxidative Stress-induced Telomere Length Shortening of Circulating Leukocyte in Patients with Obstructive Sleep Apnea
Kim Kyung Soo2, Kwak Jin Wook2, Lim Su Jin2, Park Yong Kyun2, Yang Hoon Shik2, Kim Hyun Jik1,*
1Department of Otorhinolaryngology, Seoul National University College of Medicine
2Department of Otorhinolaryngology and Head & Neck Surgery, Chung-Ang University College of Medicine, Seoul, Korea
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Abstract  

The main mechanism of pathogenesis which causes systemic complications in obstructive sleep apnea (OSA) patients is believed to be intermittent hypoxia-induced intermediary effect and it depends on the burden of oxidative stress during sleep. We aimed to search the predictive markers which reflect the burden of systemic oxidative stress in patients with OSA and whether excessive telomere length shortening is a characteristic feature that can assess oxidative stress levels. We used quantitative PCR to measure telomere length using peripheral blood genomic DNA. Telomere lengths were compared in an age- and body mass index (BMI)-dependent manner in 34 healthy volunteers and 43 OSA subjects. We also performed reactive oxygen species assay to measure the concentration of hydrogen peroxide in the peripheral blood of healthy volunteers and OSA subjects. We found that the serum concentration of hydrogen peroxide was considerably higher in OSA patients, and that this was closely related with the severity of OSA. Significantly shortened telomere length was observed in the circulating leukocytes of the peripheral blood of OSA patients, and telomere length shortening was aggravated more acutely in an age- and BMI-dependent manner. An inverse correlation was observed between the concentration of hydrogen peroxide and the telomere length of OSA patients and excessive telomere length shortening was also linked to severity of OSA. The results provided evidence that telomere length shortening or excessive cellular aging might be distinctive in circulating leukocyte of OSA patients and may be an predictive biomarker for reflect the burden of oxidative stress in the peripheral blood of OSA patients.

Keywords obstructive sleep apnea      telomere length      oxidative stress      peripheral blood      leukocyte     
Corresponding Authors: Kim Hyun Jik   
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These authors contributed equally to this work

Issue Date: 01 October 2016
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Kim Kyung Soo
Kwak Jin Wook
Lim Su Jin
Park Yong Kyun
Yang Hoon Shik
Kim Hyun Jik
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Kim Kyung Soo,Kwak Jin Wook,Lim Su Jin, et al. Oxidative Stress-induced Telomere Length Shortening of Circulating Leukocyte in Patients with Obstructive Sleep Apnea[J]. Aging and disease, 2016, 7(5): 604-613.
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http://www.aginganddisease.org/EN/10.14336/AD.2016.0215     OR     http://www.aginganddisease.org/EN/Y2016/V7/I5/604
OSA severityPatient NoH2O2RDITelomere length
Mild12.8613.31.091373
21.818.13.584852
32.036.52.821393
42.8482.512685
51.715.12.213215
62.8312.71.227582
71.816.83.15173
81.558.13.743148
91.9210.42.477892
101.047.42.808145
111.446.92.714857
Moderate12.8325.71.442105
22.5922.90.78
32.7823.70.6534477
42.7724.41.325139
53.1221.82.307201
61.8216.51.766386
71.7316.81.844485
82.9619.60.9768059
92.121.41.52453
101.9919.41.93459
112.7823.51.008529
122.4117.51.849059
131.4116.31.848659
141.9226.41.707028
152.8818.50.5581385
162.0119.21.931746
Severe13.8271.30.477892
23.238.81.046915
32.750.71.020168
44.8474.60.7610925
52.5336.30.6625695
62.9461.21.025369
72.9751.60.1077787
83.7468.71.17784
93.1358.31.041758
103.4149.70.781251
112.9839.50.442105
123.7652.50.65228
133.160.60.98
142.4330.10.73
152.3947.21.93
163.5157.30.68
Table 1  The concentration of hydrogen peroxide, Respiratory disturbance index (RDI), and mean telomere length of leukocytes in OSA patients (N=43)
Figure 1.  The concentration of hydrogen peroxide in the peripheral blood of healthy volunteers (N = 34) and OSA patients (N = 43) and correlation with severity of OSA. Mean concentration of hydrogen peroxide in the peripheral blood of healthy volunteers and OSA patients (A). Mean concentration of hydrogen peroxide in the peripheral blood of OSA patients compared by severity of OSA (11 mild OSA (circle), 16 moderate OSA (rectangle), and 16 severe OSA (diamond) patients) (B) and a significant correlation was observed between the concentration of hydrogen peroxide and the RDI of 43 OSA patients (R2=0.615) (C). Graphs show mean values. White dot: the concentration of hydrogen peroxide in healthy volunteers; black dot: the concentration of hydrogen peroxide in OSA patients (*p < .05 comparing healthy volunteers and OSA patients).
Figure 2.  Correlation between the concentration of hydrogen peroxide and telomere length in OSA patients. A significant inverse correlation was observed between the concentration of hydrogen peroxide and the telomere length of 43 OSA patients (R2=0.490) (A) and mean telomere length in healthy volunteers (N = 34) and OSA patients (N = 43) (B). Graphs show mean values. White dot: telomere length of healthy volunteers; black dot: telomere length of OSA patients (*p < .05 comparing healthy volunteers and OSA patients).
Figure 3.  Change in telomere length by age. Mean values of telomere length diminished with age in healthy volunteers (N=34), and the lowest values were observed in people older than 60 years (five were younger than 20 years old, twelve were 20-40 years, ten were 40-60 years, and seven were older than 60 years) (A). Mean values were significantly shorter in OSA patients (N=43, three who were younger than 20 years, sixteen were 20-40 years, thirteen were 40-60 years, and eleven were older than 60 years) than in healthy volunteers of the same age (B). Graphs show mean values. White dot: telomere length of healthy volunteers; black dot: telomere length of OSA patients. *p <.05 comparing healthy volunteers and OSA patients.
Figure 4.  Change in telomere length by body mass index (BMI). Mean telomere length diminished with higher BMI, and the lowest value was observed for BMI > 25 cm2/kg in healthy volunteers (eleven were less than 22.9 kg/cm2, thirteen were 23.0 to 24.9 kg/cm2, and ten were greater than 25.0 kg/cm2) (A). Mean values were significantly shorter in OSA patients (twelve were less than 22.9 kg/cm2, seventeen were 23.0 to 24.9 kg/cm2, and fourteen were greater than 25.0 kg/cm2) than in healthy volunteers in the same BMI range (B). Graphs show mean values. White dot: telomere length of healthy volunteers; black dot: telomere length of OSA patients. *p <.05 comparing healthy volunteers and OSA patients.
Figure 5.  Comparison of telomere length in the circulating leukocytes in the peripheral blood of OSA patients (N = 43) depends on OSA severity. A significant inverse correlation was observed between telomere length and the RDI of 43 OSA patients (R2=0.446).
Figure 6.  Comparison of telomere length in the circulating leukocytes in the peripheral blood of OSA patients (N = 43) depends on OSA severity. The telomere length of circulating leukocytes was significantly shorter in patients with severe OSA than patients with mild OSA (11 mild OSA (circle), 16 moderate OSA (rectangle), and 16 severe OSA (diamond) patients). Graphs show mean values, and *p < .05 compared to patients with mild OSA (A). Telomere length of circulating leukocytes in OSA patients with >20 ODI was significantly shorter than in OSA patients with <10 ODI (B). Graphs show mean value + standard deviation (SD). *p < .05 compared to OSA patients with <10 ODI.
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