title: Polymorphism of angiotensin converting enzyme, angiotensinogen, and angiotensin II type 1 receptor genes and end-stage renal failure in IgA nephropathy: IGARAS--a study of 274 Men.
abstract: The impact of renin-angiotensin system (RAS) gene polymorphism on the prognosis of IgA nephropathy (IgAN) is still debated. A longitudinal study of renal prognosis in patients with IgAN was conducted to search retrospectively for a genotype-phenotype association between RAS polymorphisms and end-stage renal failure (ESRF). A classification based on serum creatinine (S(cr)) and 24-h proteinuria (24-P) measured at the time of renal biopsy was used to estimate the risk of ESRF in IgAN: stage 1 (S(cr) </= 150 micromol/L and 24-P < 1 g), stage 2 (S(cr) > 150 micromol/L and 24-P < 1 g or S(cr) < or = 150 micromol/L and 24-P > or = 1 g), stage 3 (S(cr) > 150 micromol/L and 24-P > or = 1 g). Deletion/insertion polymorphism (D/I) of the angiotensin I converting enzyme gene, M235T polymorphism (T/M) of the angiotensinogen gene and A1166C polymorphism (C/A) of the angiotensin II type 1 receptor gene were determined in 274 Caucasian men with biopsy-proven IgAN (n = 86, 112, and 76 in stages 1, 2, and 3, respectively). Mean global follow-up was 6 +/- 5 yr after renal biopsy. For stages 1, 2, and 3, ESRF developed in 7 (8. 1%), 39 (34.8%), and 49 (64.4%) cases (P: < 0.0001), 11.7 +/- 4, 5.4 +/- 4, and 2 +/- 2 yr, respectively, after renal biopsy (P: < 0.001). The distributions of the three genotypes into the three stages were similar. Different distributions were observed when patients were grouped by stage and genotype: ID+DD: 72% in stage 1 versus 84.6% in stages 2 + 3 (P: = 0.02; kappa = 0.14); MT+TT: 66.2% in stages 1 + 2 versus 78.9% in stage 3 (P: = 0.04; kappa = 0.09); and AA+AC: 89.9% in stages 1 + 2 versus 97.4% in stage 3 (P: = 0.04; kappa = -0.1). However, with the use of the Cox proportional hazard model, none of the three genotypes was found to have predictive value for renal survival. Compared with S(cr) and 24-P, genotypes DD, TT, and AA are unlikely to serve as clinically useful predictors of ESRF in IgAN.
authors.affiliation: Department of Nephrology, University Hospital, Nancy, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Frimat
authors.affiliation: Department of Genetics, University Hospital, Nancy, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Philippe
authors.affiliation: Department of Nephrology, University Hospital, Nancy, France.
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Maghakian
authors.affiliation: Department of Genetics, University Hospital, Nancy, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Jonveaux
authors.affiliation: Department of Nephrology, University Hospital Caen, France.
authors.forename: Bruno Hurault
authors.initials: BH
authors.lastname: DE Ligny
authors.affiliation: Department of Biostatistics, University Hospital, Nancy, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Guillemin
authors.affiliation: Department of Nephrology, University Hospital, Nancy, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Kessler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000808:Angiotensinogen / Q000235:genetics*; D002648:Child; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000150:complications* / Q000235:genetics*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics*; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A