Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Level 3 207 Bouverie Street, Parkville, VIC, 3010, Australia.
Curr Allergy Asthma Rep. 2021 May 10;21(5):31. doi: 10.1007/s11882-021-01005-y.
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.
哮喘是最常见的慢性炎症性气道疾病之一。气道氧化应激定义为气道中氧化和抗氧化过程之间的失衡。有证据表明，氧化应激引起的慢性损伤可能与哮喘炎症和肺功能下降有关。鉴于其生物抗氧化功能，谷胱甘肽 S-转移酶（GST）家族中的抗氧化基因被认为与哮喘的发生和发展有关。本文旨在总结 GST 基因多态性与哮喘的关系以及与环境暴露相互作用的证据。
目前关于 GST 基因与哮喘之间关系的证据仍然薄弱或不一致。未能考虑环境暴露可能解释了这种不一致性。环境暴露与参与抗氧化途径的 GST 基因之间极有可能相互作用。根据目前的知识，GSTM1(rs366631)/T1(rs17856199)缺失基因型和 GSTP1 Val105(rs1695)基因型的携带者更容易受到环境氧化暴露的影响，患哮喘的风险更高。在不同的研究情况下，不同的环境暴露与 GST 基因之间是否存在相互作用仍存在一些疑问。GST-环境相互作用可能取决于暴露类型、哮喘表型或内型、种族以及其他复杂的基因-基因相互作用。通过定义精确的哮喘内型、涉及多个基因-基因相互作用以及增加样本量和功效，未来的研究可以得到改善。虽然有证据表明 GST 基因与环境暴露相互作用与哮喘有关，但结果并不一致。需要进一步的研究来探讨不一致的原因。
