Glutathione S-transferase polymorphisms, asthma susceptibility and confounding variables: a meta-analysis
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Glutathione S-transferase polymorphisms, asthma susceptibility and confounding variables: a meta-analysis Sara Piacentini • Renato Polimanti • Ilaria Simonelli • Silvia Donno • Patrizio Pasqualetti Dario Manfellotto • Maria Fuciarelli
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Received: 27 November 2012 / Accepted: 18 December 2012 Ó Springer Science+Business Media Dordrecht 2013
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 metaanalysis 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 (pheterogenetity \ 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. Keywords Asthmatic disease Genetic predisposition to disease GSTM1 GSTP1 GSTT1 Oxidative stress
Introduction Electronic supplementary material The online version of this article (doi:10.1007/s11033-012-2405-2) contains supplementary material, which is available to authorized users. S. Piacentini R. Polimanti M. Fuciarelli (&) Department of Biology, University of Rome ‘‘Tor Vergata’’, Via della Ricerca Scientifica 1, 00133 Rome, Italy e-mail: [email protected] I. Simonelli S. Donno P. Pasqualetti Medical Statistics and Information Technology, AFaR, Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy I. Simonelli P. Pasqualetti I.R.C.C.S. San Raffaele Pisana, Rome, Italy D. Manfellotto Clinical Pathophysiology Center, AFaR, Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy
Asthma is an inflammatory disorder of the airways characterized by reversible airway obstruction and bronchial hyper-responsiveness
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