International Journal of COPD (Jul 2022)

Serum Derivatives of Reactive Oxygen Metabolites are Associated with Severity of Chronic Obstructive Pulmonary Disease and Affected by a p53 Gene Polymorphism

  • Yamamura K,
  • Nojiri M,
  • Nishiki K,
  • Kato R,
  • Shinomiya S,
  • Takahara Y,
  • Oikawa T,
  • Ishizaki T,
  • Toga H,
  • Mizuno S

Journal volume & issue
Vol. Volume 17
pp. 1589 – 1600

Abstract

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Koichi Yamamura,* Masafumi Nojiri,* Kazuaki Nishiki, Ryo Kato, Shohei Shinomiya, Yutaka Takahara, Taku Oikawa, Takeshi Ishizaki, Hirohisa Toga, Shiro Mizuno Department of Respiratory Medicine, Kanazawa Medical University, Ishikawa, Japan*These authors contributed equally to this workCorrespondence: Shiro Mizuno, Department of Respiratory Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa, 920-0293, Japan, Tel +81-76-218-8157, Fax +81-76-286-0980, Email [email protected]: Oxidative stress is known to activate tumor suppressor p53, which inhibits cell cycle progression and induces apoptosis. Levels of p53 in lung tissues from patients with chronic obstructive pulmonary disease (COPD) are increased compared with levels in nonsmokers or smokers without emphysema. A polymorphism in p53 codon 72 (rs1042522) is associated with emphysematous changes in patients with COPD. However, whether oxidative stress in the serum is associated with the p53 polymorphism and disease severity in COPD patients is unclear.Patients and Methods: A total of 251 patients with a history of smoking more than 10 pack-years were enrolled in this study, and serum levels of derivatives of reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), and d-ROMs/BAP ratio (oxidative stress index; OSI) were measured. The percent low-attenuation area (LAA%) and cross-sectional area of the erector spinae muscles (ESMCSA) at the Th12 level were calculated from chest high-resolution computed tomography images. p53 codon 72 C/G genotyping was performed using polymerase chain reaction–restriction fragment length polymorphism analysis.Results: In patients carrying the p53 GG genotype, LAA% was significantly higher than in those carrying the CC genotype. d-ROM levels and OSI were associated with COPD severity and correlated with airflow limitation and markers of muscle atrophy (ESMCSA and creatinine/cystatin C ratio). Associations between markers of oxidative stress and COPD severity were observed primarily in patients carrying the p53 codon 72 GG genotype.Conclusion: Susceptibility to pulmonary emphysema and responses to oxidative stress may be affected by the p53 gene polymorphism.Keywords: oxidative stress, low attenuation area, sarcopenia, smoking status

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