title: Glutathione-S-transferase genes and asthma phenotypes: a Human Genome Epidemiology (HuGE) systematic review and meta-analysis including unpublished data.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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of the effects of GST genes on asthma, wheezing and bronchial hyper-responsiveness (BHR), with inclusion of unpublished data from three studies, including the large Avon Longitudinal Study of Parents and Children (ALSPAC).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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Genetic Medicine, EURAC Research, Bolzano, Italy. cosetta.minelli@eurac.edu
authors.forename: Cosetta
authors.initials: C
authors.lastname: Minelli
authors.forename: Raquel
authors.initials: R
authors.lastname: Granell
authors.forename: Roger
authors.initials: R
authors.lastname: Newson
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Rose-Zerilli
authors.forename: Maties
authors.initials: M
authors.lastname: Torrent
authors.forename: Sue M
authors.initials: SM
authors.lastname: Ring
authors.forename: John W
authors.initials: JW
authors.lastname: Holloway
authors.forename: Seif O
authors.initials: SO
authors.lastname: Shaheen
authors.forename: John A
authors.initials: JA
authors.lastname: Henderson
mesh_terms: D000328:Adult; D001249:Asthma / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007223:Infant; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D005982:Glutathione Transferase