Associations of GSTM1*0 and GSTA1*A genotypes with the risk of cardiovascular death among hemodialyses patients
1 Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Pasterova 2, 11000, Belgrade, Serbia
2 Clinical Department for Renal Diseases, Zvezdara University Medical Center, Belgrade, Serbia
3 Institute of Epidemiology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
4 Institute of Medical Physiology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
5 Department of Cardiology, Medical Center “Bezanijska Kosa”, Belgrade, Serbia
6 Clinic for Cardiovascular Diseases, Clinical Centre of Serbia, Belgrade, Serbia
7 Department of Nephrology and Hemodialysis, University Teaching Hospital Zemun, Belgrade, Serbia
8 Clinic of Endocrinology, Clinical Center of Serbia, Belgrade, Serbia
9 Faculty of Medicine, University of Belgrade, Belgrade, Serbia
BMC Nephrology 2014, 15:12 doi:10.1186/1471-2369-15-12Published: 14 January 2014
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.
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.
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.
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.