In this issue of the Journal of Human Genetics, Safarinejad et al.1 present an original case–control study globally assessing glutathione-S-transferase gene polymorphisms (GSTM1 present/null, GSTT1 present/null, GSTP1 Ile105Val) in the context of idiopathic male infertility. This study is the first to address the potential involvement of the GSTP1 Ile105Val polymorphism in idiopathic male infertility; among the original aspects of the study the synergistic effects that the authors suggested between the aforementioned three polymorphisms are worth acknowledging. Specifically, Safarinejad et al.1 suggested a positive association between male infertility and GSTM1 null genotype, GSTT1 null genotype and GSTP1 Ile/Ile status, which seem to mutually potentiate the effects of each other.

Under the light of the findings presented by Safarinejad et al.1 we performed a meta-analysis of the existing literature on the association between idiopathic male infertility and GSTM1 and GSTT1 polymorphisms. The meta-analysis was performed so as to explore whether the results reported by Safarinejad et al.1 are reproducible at the meta-analytical level. Eligible articles were identified by a search of MEDLINE bibliographical database for the period up to 15 June 2010 using combinations of the following keywords: ‘glutathione’, ‘GSTM1’, ‘GSTT1’, ‘polymorphism’, ‘genotype’, ‘idiopathic’, ‘male infertility’, ‘men’. Language restrictions were not used and two investigators (KPE and TNS), working independently, searched the literature and extracted data from each eligible case–control study. On the basis of the genotype frequencies in cases and controls, crude odds ratios (OR) and their s.e. were calculated. The ORs pertained to (i) null genotype carriers vs present (positive) genotype carriers concerning GSTM1, (ii) null genotype carriers vs present (positive) genotype carriers concerning GSTT1. After the assessment of heterogeneity, the random effects (DerSimonian Laird) model was used to calculate the pooled ORs. Between-study heterogeneity and between-study inconsistency were assessed by using Cochran Q-statistic and by estimating I2, respectively. Evidence of publication bias was determined using Egger's formal statistical test and by visual inspection of the funnel plot. For the interpretation of Egger's test, statistical significance was defined as P<0.1. In addition, sensitivity analysis excluding studies on Chinese subjects was performed so as to obtain an estimate pertaining to Caucasian populations. Meta-analysis was performed using the STATA 10.0 ‘metan’ command (STATA, College Station, TX, USA).

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