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

BMC Nephrology

Tatjana Simic²  Nada Dimkovic²  Jasmina Mimic-Oka²  Milos Zarkovic²  Steva Pljesa²  Dragan V Simic²  Slavica Radovanovic¹  Marija Pljesa-Ercegovac²  Ana Savic-Radojevic²  Jovana Jakovljevic²  Tatjana Pekmezovic²  Tatjana Damjanovic³  Sonja Suvakov² 

[1] Department of Cardiology, Medical Center “Bezanijska Kosa”, Belgrade, Serbia;Faculty of Medicine, University of Belgrade, Belgrade, Serbia;Clinical Department for Renal Diseases, Zvezdara University Medical Center, Belgrade, Serbia

关键词: Oxidative stress;    Mortality risk;    Polymorphism;    ESRD;    Cardiovascular disease;   

Others  :  1082747
DOI  :  10.1186/1471-2369-15-12

 received in 2013-05-13, accepted in 2013-12-24,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Suvakov et al.; licensee BioMed Central Ltd.

【 图 表 】

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