title: Influence of genetic polymorphisms of the renin-angiotensin system on IgA nephropathy.
abstract: 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.
authors.affiliation: Department of Nephrology and Rheumatology, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Bantis
authors.forename: K
authors.initials: K
authors.lastname: Ivens
authors.forename: W
authors.initials: W
authors.lastname: Kreusser
authors.forename: M
authors.initials: M
authors.lastname: Koch
authors.forename: N
authors.initials: N
authors.lastname: Klein-Vehne
authors.forename: B
authors.initials: B
authors.lastname: Grabensee
authors.forename: P
authors.initials: P
authors.lastname: Heering
mesh_terms: D005260:Female; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012084:Renin-Angiotensin System / Q000235:genetics*