Glutathione-S-Transferase M1 and T1 Null Genotypes Are Associated with Hypertension Risk: A Systematic Review and Meta-Analysis of 12 Studies

Oxidative stress is known to be implicated in the pathogenesis of essential hypertension. Glutathione-S-transferase (GST) enzymes are key components of cellular defense against oxidative stress. The present study aimed to clarify the association between polymorphisms in GST and risk of essential hypertension using a meta-analysis of published studies. PubMed-Medline, Ovid-EMBASE, HuGE Navigator and SCOPUS databases were searched to identify case-control studies that examined the association of GST polymorphisms and hypertension. Data were extracted using standardized methods. Combined odds ratios (OR) with 95 % confidence intervals (CI) for the association of polymorphisms with hypertension were calculated using a fixed effect approach and under dominant, recessive, additive and over-dominant models of inheritance. A total of 12 studies comprising 2,040 cases and 2,462 controls fulfilled the inclusion criteria. GSTM1 (presence/null), GSTT1 (presence/null) and GSTP1 (Ile105Val; rs1695) polymorphisms were evaluated. Meta-analysis revealed significant associations between the null genotypes of GSTM1 (OR: 1.22; 95 % CI: 1.08-1.39; p=0.002) and GSTT1 (OR: 1.30; 95% CI: 1.13-1.50; p=0.0003) and risk of hypertension. The observed associations were robust in sensitivity analyses. However, no significant association was found for the rs1695 polymorphism under all assessed modes of inheritance. Findings of the present meta-analysis demonstrated that GSTM1 and GSTT1 null genotypes may serve as predisposing factors for essential hypertension. Further studies are warranted to validate this association, and also to explore if these null genotypes are in linkage with other hypertension susceptibility polymorphisms.