Effects of the genetic polymorphisms of the renin-angiotensin system on focal segmental glomerulosclerosis.
OBJECTIVE
We analyzed the influence of angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T and angiotensin-II-type-1 receptor (AT1R) A1166C genetic polymorphisms on the clinical course of focal segmental glomerulosclerosis (FSGS).


METHODS
This study consisted of 71 patients with nephrotic syndrome due to biopsy proven FSGS and 100 healthy controls. According to the slope of the reciprocal serum creatinine (1/Cr, >or= or <-0.1 dl x mg(-1) x year(-1)) patients were classified into group A (slow progressors, n = 50) and group B (fast progressors, n = 21). Genotyping was performed using polymerase chain reaction (PCR).


RESULTS
There were no relevant differences in the allele frequencies of the investigated polymorphisms between patients with FSGS and controls. Patients carrying the T- allele of the AGT polymorphism required a larger number of antihypertensive agents (MM: 1.35 +/- 1.0 vs. MT/TT: 2.0 +/- 1.2, p < 0.05). The ACE-ID/DD genotypes were more frequently found in patients with fast progression (group A: II: 38.0%, ID/DD: 62.0% vs. group B: II: 14.3%, ID/DD: 85.7%, p < 0.05). The AT1R-A1166C polymorphism was not associated with any of the parameters studied.


CONCLUSIONS
The course of FSGS is in part genetically determined by polymorphisms of the renin-angiotensin-system. The ACE-I/D polymorphism was shown to be a risk factor of progression of renal disease and the AGT-M235T polymorphism was associated with the severity of arterial hypertension.
Luther
Y
Y
Department of Nephrology and Rheumatology, Heinrich-Heine-University, Düsseldorf, Germany.
Bantis
C
C
Ivens
K
K
Fehsel
K
K
Kolb-Bachhofen
V
V
Heering
P
P
D000328:Adult; D000809:Angiotensins / Q000235:genetics / Q000502:physiology; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000235:genetics; D007674:Kidney Diseases / Q000235:genetics; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000502:physiology; D011110:Polymorphism, Genetic / Q000502:physiology*; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000502:physiology; D012084:Renin-Angiotensin System / Q000235:genetics* / Q000502:physiology
D000809:Angiotensins; D044140:Receptor, Angiotensin, Type 1; D007703:Peptidyl-Dipeptidase A