Department of Respiratory Medicine, Kanazawa Medical University, Ishikawa, Japan.
Int J Chron Obstruct Pulmon Dis. 2022 Jul 13;17:1589-1600. doi: 10.2147/COPD.S366792. eCollection 2022.
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.
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 (ESM) at the Th 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.
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 (ESM 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.
Susceptibility to pulmonary emphysema and responses to oxidative stress may be affected by the p53 gene polymorphism.
氧化应激已知可激活肿瘤抑制因子 p53，p53 可抑制细胞周期进程并诱导细胞凋亡。与不吸烟者或非肺气肿吸烟者相比，慢性阻塞性肺疾病（COPD）患者的肺组织中 p53 水平升高。p53 密码子 72 （rs1042522）的多态性与 COPD 患者的肺气肿变化有关。然而，血清中的氧化应激是否与 COPD 患者的 p53 多态性和疾病严重程度有关尚不清楚。
共纳入 251 例吸烟超过 10 包年的患者，测量血清中活性氧代谢物衍生物（d-ROMs）、生物抗氧化潜能（BAP）和 d-ROMs/BAP 比值（氧化应激指数；OSI）水平。通过胸部高分辨率计算机断层扫描图像计算低衰减区百分比（LAA%）和 Th 水平竖脊肌的横截面积（ESM）。使用聚合酶链反应-限制性片段长度多态性分析进行 p53 密码子 72 C/G 基因分型。
携带 p53 GG 基因型的患者的 LAA%明显高于携带 CC 基因型的患者。d-ROM 水平和 OSI 与 COPD 严重程度相关，与气流受限和肌肉萎缩标志物（ESM 和肌酐/胱抑素 C 比值）相关。在携带 p53 密码子 72 GG 基因型的患者中，观察到氧化应激标志物与 COPD 严重程度之间的相关性。
对肺气肿的易感性和对氧化应激的反应可能受 p53 基因多态性的影响。
