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 of end-stage renal disease (ESRD) and promote a more rapid progression to ESRD in patients with renal diseases. Genes encoding for angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and aldosterone synthase (CYP11B2) are candidates for abnormal blood pressure regulation.


METHODS
Genotyping was performed in 327 control subjects and 260 ESRD patients for the M235T-AGT, the insertion/deletion (I/D)-ACE, and the -344T/C-CYP11B2 gene polymorphisms using polymerase chain reaction, gel analysis, and appropriate restriction digest when required.


RESULTS
Genotype frequencies did not differ significantly between ESRD patients and controls. When ESRD diabetic subjects were compared with diabetic patients without nephropathy, the prevalence of the AGT-MM genotype was lower (28.1 vs. 52.8%, P < 0.01), while the AGT-TT genotype was higher (15.6 vs. 2.7%, P < 0.05). The AGT-TT genotype was associated with a faster progression to ESRD in patients with glomerulonephritis (P < 0.05). In the total ESRD population, progression of renal disease was faster with the ACE-DD than with the DI and II alleles (P < 0.05). This association was particularly strong when the interaction with the AGT genotype was analyzed, with a rapid progression in ACE-DD as compared with ACE-DI and II in patients with the AGT-MM genotype (P < 0.01).


CONCLUSIONS
Susceptibility for ESRD and faster progression to ESRD are linked 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 genes for further understanding of the interindividual differences in the development and course of ESRD.
Lovati
E
E
Division of Nephrology and Hypertension, Inselspital, University of Berne, Berne, Switzerland.
Richard
A
A
Frey
B M
BM
Frey
F J
FJ
Ferrari
P
P
D000328:Adult; D000368:Aged; D000808:Angiotensinogen / Q000235:genetics; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics; D003928:Diabetic Nephropathies / Q000235:genetics / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005921:Glomerulonephritis / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D012016:Reference Values; D012084:Renin-Angiotensin System / Q000235:genetics*; D013997:Time Factors
D000808:Angiotensinogen; D019405:Cytochrome P-450 CYP11B2; D007703:Peptidyl-Dipeptidase A