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

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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.

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Acknowledgments

This study was supported by RSA Grant 2009 from University of Rome “Tor Vergata” and by PRIN 2009-2011 (prot. n. 200975T9EW) from MIUR.

Conflict of interest

The authors stated that there are no conflicts of interest regarding the publication of this article.

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Authors and Affiliations

  1. Department of Biology, University of Rome “Tor Vergata”, Via della Ricerca Scientifica 1, 00133, Rome, Italy

    Sara Piacentini, Renato Polimanti & Maria Fuciarelli

  2. Medical Statistics and Information Technology, AFaR, Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy

    Ilaria Simonelli, Silvia Donno & Patrizio Pasqualetti

  3. I.R.C.C.S. San Raffaele Pisana, Rome, Italy

    Ilaria Simonelli & Patrizio Pasqualetti

  4. Clinical Pathophysiology Center, AFaR, Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy

    Dario Manfellotto

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  1. Sara Piacentini
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Supplementary material 1 (DOC 88 kb)

Supplemental Figure 1

Funnel plot analysis to detect publication bias in study on GSTM1. Each point represents an individual study for the indicated association (TIFF 3113 kb)

Supplemental Figure 2

Cumulative forest plot to detect temporal effect in study on GSTM1 (TIFF 2324 kb)

Supplemental Figure 3

Funnel plot analysis to detect publication bias in study on GSTM1. Each point represents an individual study for the indicated association (TIFF 3113 kb)

Supplemental Figure 4

Cumulative forest plot to detect temporal effect in study on GSTT1 (TIFF 2183 kb)

Supplemental Figure 5

Funnel plot analysis to detect publication bias in study on GSTP1 (dominant genetic model). Each point represents an individual study for the indicated association (TIFF 3113 kb)

Supplemental Figure 6

Funnel plot analysis to detect publication bias in study on GSTP1 (recessive genetic model). Each point represents an individual study for the indicated association (TIFF 3113 kb)

Supplemental Figure 7

Cumulative forest plot to detect temporal effect in study on GSTP1 (dominant genetic model) (TIFF 2319 kb)

Supplemental Figure 8

Cumulative forest plot to detect temporal effect in study on GSTP1 (recessive genetic model) (TIFF 2335 kb)

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Piacentini, S., Polimanti, R., Simonelli, I. et al. Glutathione S-transferase polymorphisms, asthma susceptibility and confounding variables: a meta-analysis. Mol Biol Rep 40, 3299–3313 (2013). https://doi.org/10.1007/s11033-012-2405-2

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