Glutathione S-transferase polymorphisms, asthma susceptibility and confounding variables: a meta-analysis

Abstract

Oxidative stress is one of the main risk factors for asthma development. Glutathione S-transferases play an important role in antioxidant defences and may influence asthma susceptibility. In particular, GSTM1 and GSTT1 positive/null genotypes and the GSTP1 Ile105 Val polymorphism have been analyzed in a number of genetic association studies, with conflicting outcomes. Two previous meta-analyses have attempted to clarify the associations between GST genes and asthma, but these studies have also showed contrasting results. Our aim was to perform a meta-analysis that included independent genetic association studies on GSTM1, GSTP1, and GSTT1, evaluating also the effect of potential confounding variables (i.e. ethnicity, population age, and urbanization). Systematic review and meta-analysis of the effects of GST genes on asthma were conducted. The meta-analyses were performed using a fixed or, where appropriate, random effects model. The meta-analysis of the GSTM1 (n = 35), GSTT1 (n = 31) and GSTP1 (n = 28) studies suggests that no significant associations with asthma susceptibility were observed for GSTM1 and GSTP1 gene polymorphisms, whereas a significant outcome was detected for the GSTT1 positive/null genotype (pooled OR = 1.33, 95 %CI = 1.10-1.60). However, high between-study heterogeneity was identified in all the general analyses (p heterogenetity < 0.05). The stratification analysis seems to explain the heterogeneity only in few cases. This picture is probably due to the interactive process of genetics and environment that characterizes disease pathogenesis. Further studies on interactions of GST genes with the potential oxidative stress sources and with other antioxidant genes are needed to explain the role of GST enzymes in asthma.

Association of Single Nucleotide Polymorphisms in Toll-like Receptor Genes With Asthma Risk: a Systematic Review and Meta-analysis

“…These potential confounding factors may interact with TLR polymorphisms to moderate asthma susceptibility. Genetic associations were shown to be significantly influenced by age75,76,77,78 likely because some genes are expressed in adults and not expressed in children and vice versa . Observational studies showed that the prevalence of asthma has increased during the last decade due to environmental factors 3.…”

Neonatal jaundice and risks of childhood allergic diseases: a population-based cohort study

“…Glutathione S-transferases are a large family of proteins that participate in the metabolism of reactive oxygen species and detoxification of xenobiotics. Polymorphisms in the genes of glutathione S-transferase indicate an association between neonatal hyperbilirubinemia and allergy, asthma, and AD (27)(28)(29)(30). Bilirubin may increase intestinal protein permeability and may be associated with a higher risk of developing an allergy to cow milk protein in young infants (31).…”

A pooled multisite analysis of the effects of atopic medical conditions in glioma risk in different ethnic groups

“…The prevalence of atopic conditions also varies between ethnicities, though the causes of these differences are unclear [17]. There are studies suggesting there are associations between gene polymorphisms and the presence of atopic conditions [18–20]. Thus, the associations between atopic conditions and different ethnicities may be biologically based.…”