Genetic polymorphisms of the renin-angiotensin-aldosterone system in end-stage renal disease

Background. Hypertension contributes to the progression to renal failure. A genetic susceptibility to hypertension may predispose to the development o f end-stage renal disease (ESRD) and promote a more rapid progression to ES RD in patients with renal diseases. Genes encoding for angiotensinogen (AGT ), angiotensin-converting enzyme (ACE), and aldosterone synthase (CYPIIB2) are candidates for abnormal blood pressure regulation. Methods. Genotyping was performed in 327 control subjects and 260 ESRD pati ents for the M235T-AGT. the insertion/ deletion (IID)-ACE, and the -344T/C- CYPIIB2 gene polymorphisms using polymerase chain reaction, gel analysis, a nd appropriate restriction digest when required. Results. Genotype frequencies did not differ significantly between ESRD pat ients and controls. When ESRD diabetic subjects were compared with diabetic patients without nephropathy, the prevalence of the AGT-MM genotype was lo wer (28.1 vs. 52.8%, P < 0.01), while the AGT-TT genotype was higher (15.6 vs. 2.7%, P < 0.05). The ACT-TT genotype was associated with a faster progr ession to ESRD in patients with glomerulonephritis (P < 0.05). In the total ESRD population, progression of renal disease was faster with the ACE-DD t han with the DI and II alleles (P <less than> 0.05). This association was p articularly strong when the interaction with the AGT genotype was analyzed, with a rapid progression in ACE-L)D as compared with ACE-D( and II in pati ents with the AGT-MM genotype (P < 0.01). Conclusions. Susceptibility for ESRD and faster progression to ESRD are lin ked with the AGT genotype in diabetic patients. Faster progression to ESRD is associated with the ACE genotype when the total population with ESRD and with the AGT genotype when patients with glomerulonephritis are considered . Thus, genes of the renin-angiotensin aldosterone system are candidate gen es for further understanding of the interindividual differences in the deve lopment and course of ESRD.