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

Abstract

BackgroundThe 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.MethodsTotal 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.ResultsGSTM1-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.ConclusionsCombined 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.

GSTA1 gene variation associated with gestational hypertension and its involvement in pregnancy-related pathogenic conditions

“…However, those that exist indicate that the GSTA1*-69C/T polymorphism is a potential genetic marker for cardiovascular death risk in end-stage renal disease patients [33], and a genetic risk factors for essential hypertension [34]. In the study of Oniki and collaborators, GSTA1*-69C was positively associated with the arterial hypertension in a Japanese sample.…”

Oxidative Status before and after Renal Replacement Therapy: Differences between Conventional High Flux Hemodialysis and on-Line Hemodiafiltration

“…Moreover, low levels of TAC in hemodialysis patients due to low levels of bilirubin [40] have been related to increased mortality. Also, polymorphisms in glutathione S-transferase M1, which are associated with a reduction in glutathione levels, have been described in hemodialysis [41] to favor oxidative damage in DNA and reduces survival [42] from all-cause and cardiovascular mortality over 25 years of follow-up [43].…”

Glutathione S-Transferase Deletion Polymorphisms in Early-Onset Psychotic and Bipolar Disorders: A Case-Control Study

“…It has recently been suggested that oxidative stress might mediate vascular damage in patients with psychosis, and it has been established that patients with psychosis are at higher risk for developing cardiovascular diseases 45 and diabetes mellitus. 46 GSTM1-null and GSTT1-null genotypes have already been recognized as potential determinants of higher risk for coronary artery disease 47 and even cardiovascular death, 48 as well as an increased susceptibility to advanced atherosclerosis 49 in patients without mental psychiatric diseases. As a result, it seems reasonable to assume that these genetic polymorphisms might make certain contributions to the development and progression of mental disorders.…”