Associations of GSTM1*0 and GSTA1*Agenotypes with the risk of cardiovascular death among hemodialyses patients
| Autor: | Slavica Radovanovic, Sonja Suvakov, Milos Zarkovic, Steva Pljesa, Marija Pljesa-Ercegovac, Jasmina Mimic-Oka, Tatjana Pekmezovic, Tatjana Simic, Tatjana Damjanovic, Nada Dimkovic, Jovana Jakovljevic, Ana Savic-Radojevic, D.V. Simic |
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| Rok vydání: | 2014 |
| Předmět: |
Genetic Markers
Male Nephrology medicine.medical_specialty medicine.medical_treatment Single-nucleotide polymorphism Disease 030204 cardiovascular system & hematology 03 medical and health sciences 0302 clinical medicine Renal Dialysis Risk Factors Internal medicine Genotype medicine Humans Genetic Predisposition to Disease Myocardial infarction ESRD Polymorphism neoplasms Survival rate Mortality risk Genetic Association Studies Glutathione Transferase 030304 developmental biology 0303 health sciences integumentary system Proportional hazards model business.industry Incidence Middle Aged Cardiovascular disease medicine.disease 3. Good health Survival Rate Death Sudden Cardiac Oxidative stress Cardiovascular Diseases Female Hemodialysis business Serbia Research Article |
| Zdroj: | BMC Nephrology |
| ISSN: | 1471-2369 |
| DOI: | 10.1186/1471-2369-15-12 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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