Genetic variation and gene expression in antioxidant related enzymes and risk of COPD: a systematic review

Abstract

Background: Observational epidemiological studies of dietary antioxidant intake, serum antioxidant concentration and lung outcomes suggest that lower levels of antioxidant defences are associated with decreased lung function. Another approach to understanding the role of oxidant/antioxidant imbalance in the risk of chronic obstructive pulmonary disease (COPD) is to investigate the role of genetic variation in antioxidant enzymes, and indeed family based studies suggest a heritable component to lung disease. Many studies of the genes encoding antioxidant enzymes have considered COPD or COPD related outcomes, and a systematic review is needed to summarise the evidence to date, and to provide insights for further research. Methods: Genetic association studies of antioxidant enzymes and COPD/COPD related traits, and comparative gene expression studies with disease or smoking as the exposure were systematically identified and reviewed. Antioxidant enzymes considered included enzymes involved in glutathione metabolism, in the thioredoxin system, superoxide dismutases (SOD) and catalase. Results: A total of 29 genetic association and 15 comparative gene expression studies met the inclusion criteria. The strongest and most consistent effects were in the genes GCL, GSTM1, GSTP1 and SOD3. This review also highlights the lack of studies for genes of interest, particularly GSR, GGT and those related to TXN. There were limited opportunities to evaluate the contribution of a gene to disease risk through synthesis of results from different study designs, as the majority of studies considered either association of sequence variants with disease or effect of disease on gene expression. Conclusion: Network driven approaches that consider potential interaction between and among genes, smoke exposure and antioxidant intake are needed to fully characterise the role of oxidant/antioxidant balance in pathogenesis.

Extracellular superoxide dismutase protects against pulmonary emphysema by attenuating oxidative fragmentation of ECM

“…Acute loss of SOD3 in adult mice causes death, whereas low mortality rates are seen in SOD3-overexpressing animals exposed to hyperoxia, suggesting an essential role of SOD3 for survival (3,4). Accumulating evidence shows that SOD3 polymorphism is associated with a decline in lung function in rodents and humans, and susceptibility to COPD, which may be a result of alteration of its encoding protein structure, function, and level (5)(6)(7)(8)(9)(10)(11)(12)(13)(14). However, it is unclear whether endogenous SOD3 participates in the development/ progression of the inflammatory response, leading to COPD/ emphysema.…”

Sarsaparilla (Smilax Glabra Rhizome) Extract Inhibits Cancer Cell Growth by S Phase Arrest, Apoptosis, and Autophagy via Redox-Dependent ERK1/2 Pathway

“…4B). Among oxidative stress-related genes, GCLC, GCLM, GPX5, GPX2, and G6PD have been implicated in GSH metabolism (23); therefore, we evaluated the intercellular reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, one hallmark of oxidative stress (24). We found AGS and HT-29 cells suffered a marked GSH/GSSG imbalance following SW treatment for 0.5 and 24 hours (Fig.…”

Glutathione peroxidase-1 as a novel therapeutic target for COPD

“…65 Gpx activity is significantly reduced in smokers and subjects with COPD, highlighting its prominent role in lung antioxidant defense. 63 With respect to reduced Gpx activity in COPD patients and smokers, erythrocyte Gpx activity was significantly lower in patients with severe COPD compared with patients with moderate COPD. 68 In addition, Gpx activity was decreased in plasma from COPD patients 69 and total blood from smokers and ex-smokers.…”

“…60 It has been shown that Gpx-2 is induced in the lungs of mice in response to cigarette smoke and that basal and CS-inducible expression of Gpx-2 are directly dependent on Nrf2. 61,62 In humans, Gpx-1 has been shown to be increased in COPD, 63 and Gpx-2 showed a three-to five-fold up-regulation in epithelial cells of smokers compared with nonsmokers. [64][65][66] Gpx-3 showed a two-fold up-regulation in epithelial cells of smokers compared with nonsmokers.…”