Glutathione S-Transferase Gene Associations and Gene-Environment Interactions for Asthma

Asthma is one of the most common chronic inflammatory airway diseases. Airway oxidative stress is defined as an imbalance between oxidative and antioxidative processes in the airways. There is evidence that chronic damage caused by oxidative stress may be involved in asthmatic inflammation and reduced lung function. Given their biological antioxidant function, the antioxidant genes in the glutathione S-transferase (GST) family are believed to be associated with development and progression of asthma. This review aims to summarize evidence on the relationship between GST gene polymorphisms and asthma and interactions with environmental exposures.

The current evidence on the association between GST genes and asthma is still weak or inconsistent. Failure to account for environmental exposures may explain the lack of consistency. It is highly likely that environmental exposures interact with GST genes involved in the antioxidant pathway. According to current knowledge, carriers of GSTM1(rs366631)/T1(rs17856199) null genotypes and GSTP1 Val105 (rs1695) genotypes are more susceptible to environmental oxidative exposures and have a higher risk of asthma. Some doubt remains regarding the presence or absence of interactions with different environmental exposures in different study scenarios. The GST-environment interaction may depend on exposure type, asthma phenotype or endotype, ethnics, and other complex gene-gene interaction. Future studies could be improved by defining precise asthma endotypes, involving multiple gene-gene interactions, and increasing sample size and power. Although there is evidence for an interaction between GST genes, and environmental exposures in relation to asthma, results are not concordant. Further investigations are needed to explore the reasons behind the inconsistency.