• Chest · Jul 2017

    p53 signaling pathway polymorphisms associated with emphysematous changes in COPD patients.

    • Shiro Mizuno, Takeshi Ishizaki, Maiko Kadowaki, Masaya Akai, Kohei Shiozaki, Masaharu Iguchi, Taku Oikawa, Ken Nakagawa, Kazuhiro Osanai, Hirohisa Toga, Jose Gomez-Arroyo, Donatas Kraskauskas, Carlyne D Cool, Herman J Bogaard, and Norbert F Voelkel.
    • Department of Respiratory Medicine, Kanazawa Medical University, Ishikawa, Japan. Electronic address: shirotan@qf6.so-net.ne.jp.
    • Chest. 2017 Jul 1; 152 (1): 58-69.

    BackgroundThe p53 signaling pathway may be important for the pathogenesis of emphysematous changes in the lungs of smokers. Polymorphism of p53 at codon 72 is known to affect apoptotic effector proteins, and the polymorphism of mouse double minute 2 homolog (MDM2) single nucleotide polymorphism (SNP)309 is known to increase MDM2 expression. The aim of this study was to assess polymorphisms of the p53 and MDM2 genes in smokers and confirm the role of SNPs in these genes in the pathogenesis of pulmonary emphysema.MethodsThis study included 365 patients with a smoking history, and the polymorphisms of p53 and MDM2 genes were identified. The degree of pulmonary emphysema was determined by means of CT scanning. SNPs, MDM2 mRNA, and p53 protein levels were assessed in human lung tissues from smokers. Plasmids encoding p53 and MDM2 SNPs were used to transfect human lung fibroblasts (HLFs) with or without cigarette smoke extract (CSE), and the effects on cell proliferation and MDM2 promoter activity were measured.ResultsThe polymorphisms of the p53 and MDM2 genes were associated with emphysematous changes in the lung and were also associated with p53 protein and MDM2 mRNA expression in the lung tissue samples. Transfection with a p53 gene-coding plasmid regulated HLF proliferation, and the analysis of P2 promoter activity in MDM2 SNP309-coding HLFs showed the promoter activity was altered by CSE.ConclusionsOur data demonstrated that p53 and MDM2 gene polymorphisms are associated with apoptotic signaling and smoking-related emphysematous changes in lungs from smokers.Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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