Influence of Genetic Polymorphisms of the Renin-Angiotensin System on IgA Nephropathy

• Published in: American journal of nephrology Vol. 24; no. 2; pp. 258 - 267
• Main Authors: Bantis, C., Ivens, K., Kreusser, W., Koch, M., Klein-Vehne, N., Grabensee, B., Heering, P.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.03.2004; S. Karger AG
• Subjects: Biological and medical sciences; Female; Glomerulonephritis, IGA - genetics; Humans; Male; Medical sciences; Nephrology. Urinary tract diseases; Original Report: Patient-Oriented, Translational Research; Polymorphism, Genetic; Renin-Angiotensin System - genetics; Angiotensin-converting enzyme I/D polymorphism; Angiotensinogen M235T polymorphism; IgA nephropathy; Angiotensin II-type 1 receptor A1166C polymorphism; ACE inhibitors; Genetic polymorphisms; Nephrology; Peptides; Enzyme; IgA Nephropathy; Urology; Peptidases; Renin angiotensin system; Type; Peptidyl-dipeptidase A; Angiotensinogen; Hydrolases; Peptidyl-dipeptidases; Genetics; Influence; Angiotensin II; ACE inhibitor; Polymorphism
• ISSN: 0250-8095; 1421-9670
• DOI: 10.1159/000077398

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 (AT 1 R) 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.