Institute of Genetic Medicine, EURAC Research, Bolzano, Italy.
Int J Epidemiol. 2010 Apr;39(2):539-62. doi: 10.1093/ije/dyp337. Epub 2009 Dec 23.
Oxidative stress is thought to be involved in the pathogenesis of asthma. Glutathione-S-transferase (GST) enzymes, which play an important role in antioxidant defences, may therefore influence asthma risk. Two common deletion polymorphisms of GSTM1 and GSTT1 genes and the GSTP1 Ile105Val polymorphism have been associated with asthma in children and adults, but results are inconsistent across studies.
Systematic review and meta-analysis of the effects of GST genes on asthma, wheezing and bronchial hyper-responsiveness (BHR), with inclusion of unpublished data from three studies, including the large Avon Longitudinal Study of Parents and Children (ALSPAC). Random effect or fixed effect models were used as appropriate, and sensitivity analyses were performed to assess the impact of study characteristics and quality on pooled results.
The meta-analyses of GSTM1 (n = 22 studies) and GSTT1 (n = 19) showed increased asthma risk associated with the null genotype, but there was extreme between-study heterogeneity and publication bias and the association disappeared when meta-analysis was restricted to the largest studies. Meta-analysis of GSTP1 Ile105Val (n = 17) and asthma suggested a possible protective effect of the Val allele, but heterogeneity was extreme. Few studies evaluated wheezing and BHR and most reported no associations, although weak evidence was found for positive associations of GSTM1 null and GSTP1 Val allele with wheezing and a negative association of GSTP1 Val allele with BHR.
Our findings do not support a substantial role of GST genes alone in the development of asthma. Future studies of large size should focus on interactions of GST genes with environmental oxidative exposures and with other genes involved in antioxidant pathways. Quality of study conduct and reporting needs to be improved to increase credibility of the evidence accumulating over time.
氧化应激被认为与哮喘的发病机制有关。谷胱甘肽-S-转移酶（GST）酶在抗氧化防御中发挥重要作用，因此可能影响哮喘风险。GSTM1 和 GSTT1 基因的两个常见缺失多态性和 GSTP1 Ile105Val 多态性与儿童和成人哮喘有关，但研究结果不一致。
系统评价和荟萃分析 GST 基因对哮喘、喘息和支气管高反应性（BHR）的影响，包括三项研究的未发表数据，其中包括大型雅芳纵向父母和儿童研究（ALSPAC）。随机效应或固定效应模型根据需要使用，并进行敏感性分析，以评估研究特征和质量对汇总结果的影响。
GSTM1（n = 22 项研究）和 GSTT1（n = 19 项）的荟萃分析显示，与空基因型相比，哮喘风险增加，但存在极端的研究间异质性和发表偏倚，当荟萃分析仅限于最大的研究时，这种关联消失了。GSTP1 Ile105Val（n = 17）与哮喘的荟萃分析表明，Val 等位基因可能具有保护作用，但异质性极高。很少有研究评估喘息和 BHR，大多数研究未发现关联，但发现 GSTM1 空基因型和 GSTP1 Val 等位基因与喘息呈正相关，GSTP1 Val 等位基因与 BHR 呈负相关的微弱证据。
我们的研究结果不支持 GST 基因单独在哮喘发展中的重要作用。未来的大型研究应侧重于 GST 基因与环境氧化应激暴露以及与抗氧化途径中其他基因的相互作用。需要提高研究实施和报告的质量，以提高随着时间的推移积累的证据的可信度。
