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Background  The presence of glutathione transferase (GST) M1 null genotype ( GSTM1 -null) in end-stage renal disease (ESRD) patients is associated with lower overall survival rate in comparison to those with  GSTM1 -active variants. We examined association between  GSTM1  and  GSTT1  deletion polymorphisms as well as SNPs in  GSTA1/ rs3957357 and  GSTP1 /rs1695 genes with overall and cause-specific cardiovascular mortality in ESRD patients.    Methods  Total of 199 patients undergoing hemodialysis were included in the study. Median value of time elapsed from dialysis initiation until the death, or the end of follow-up was 8 ± 5 years. The effect of  GSTM1, GSTT1, GSTP1  and  GSTA1  gene polymorphisms on predicting overall and specific cardiovascular outcomes (myocardial infarction, MI or stroke) was analyzed using Cox regression model, and differences in survival were determined by Kaplan-Meier.    Results   GSTM1 -null genotype in ESRD patients was found to be independent predictor of overall and cardiovascular mortality. However, after false discovery rate and Bonferroni corrections this effect was lost. The borderline effect modification by wild-type  GSTA1*A/*A  genotype on associations between  GSTM1 -null and analyzed outcomes was found only for death from stroke. Homozygous carriers of combined  GSTM1*0/GSTA1*A  genotype exhibited significantly shorter time to death of stroke or MI in comparison with carriers of either  GSTM1 -active or at least one  GSTA1*B  gene variant. The best survival rate regarding cardiovascular outcome was found for ESRD patients with combined  GSTM1 -active and mutant  GSTA1*B/*B  genotype.    Conclusions  Combined  GSTM1*0/GSTA1*A  genotypes might be considered as genetic markers for cardiovascular death risk in ESRD patients, which may permit targeting of preventive and early intervention.

Associations of GSTM1*0 and GSTA1*Agenotypes with the risk of cardiovascular death among hemodialyses patients

Associations of GSTM10 and GSTA1Agenotypes with the risk of cardiovascular death among hemodialyses patients