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.
CONCLUSIONS: 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.