Influence of genetic polymorphisms of the renin-angiotensin system on IgA nephropathy.
BACKGROUND
We evaluated the impact of the three major genetic polymorphisms of the renin-angiotensin system [angiotensinogen (AGT) gene M235T, angiotensin-converting enzyme (ACE) gene-I/D and angiotensin II-type 1 receptor (AT1R) gene A1166C polymorphisms] as risk factors in IgA nephropathy.


METHODS
The clinical course of 107 patients with biopsy proven IgA nephropathy followed up for 6.6 +/- 5.8 years was examined. The genetic polymorphisms were determined by PCR amplification.


RESULTS
The allele frequencies of the polymorphisms studied were similar in patients and control subjects. AGT-M235T genotype was associated with the presence of nephrotic syndrome (p < 0.05), correlated to the number of antihypertensive drugs agents taken (p < 0.01) and influenced the rate of deterioration of renal function (p < 0.05). Combined analysis of AGT-M235T and ACE-I/D polymorphisms detected an interaction on affecting progression (p < 0.05). ACE-inhibition had a more pronounced effect in certain AGT-M235T and ACE-I/D genotypes (p < 0.05) and their combined analysis showed a synergistic effect (p < 0.01). No association between AT(1)R-A1166C polymorphism and any of the parameters studied was observed.


CONCLUSIONS
Our results suggest that angiotensinogen-M235T polymorphism is an important marker of progression in IgA nephropathy in Caucasian patients, especially when analyzed in combination with ACE-I/D polymorphism.
Bantis
C
C
Department of Nephrology and Rheumatology, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
Ivens
K
K
Kreusser
W
W
Koch
M
M
Klein-Vehne
N
N
Grabensee
B
B
Heering
P
P
D005260:Female; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012084:Renin-Angiotensin System / Q000235:genetics*