RAS and ecNOS Gene Polymorphisms in Dialysis Patients: Influence on Survival

Survival for patients with end-stage renal disease is influenced by many environmental and genetic factors. In this study, we aimed to define influence of angiotensin-converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 and 2 (ATR1 and ATR2) receptors in the renin-angiotensin system (RAS), as well as endothelial constitutive nitric oxide synthase (ecNOS) gene polymorphisms on patient survival, in a population of Turkish patients with end-stage renal disease. One hundred and sixty-seven patients followed either by hemodialysis (n: 91) or continuous ambulatory peritoneal dialysis (n: 76) were included in this study. Genotyping was performed for the insertion/deletion of ACE (I/D), AGT (M➝T, 235), ATR1 (A➝C, 1166), ATR2 (A➝G, 1223), and ecNOS (b➝a, intron 4) gene polymorphisms. Retrospective data for the prior 12 months, including clinical and demographic data were collected and analyzed. Polymorphism percentages were ATR1:AA/AC/CC, 64%, 34.7%, and 1.3%; ATR2: AA/AC/CC, 17.7%, 32%, and 50.3%; AGT:TT/TC/CC, 32%, 66%, and 2%; ACE:DD/ID/II, 51.4%, 38.5%, and 10.1%; and ecNOS:aa/ab/bb, 7.6%, 24.3%, and 68.1%, respectively. Our analyzes revealed that; in patients who were recieving hemodialysis for more than 5 years (n:85) prevalence of the bb variant of ecNOS gene was higher (73.4% vs 63.9%, P < 0.05) than the ones with shorter dialysis duration (n:82). There were no statistically significant differences between groups in terms of RAS gene polymorphisms. Further analysis revealed that bb variant was also more prevalent in patients with longterm survival with known adverse RAS variants. We conclude therefore, that the high prevalence of the bb variant of the ecNOS gene polymorphism seen in Turkish patients with end-stage renal disease undergoing dialysis possibly balances increased RAS activity and influences long-term survival.