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.
Fiche publication
Date publication
novembre 2000
Journal
Journal of the American Society of Nephrology : JASN
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GUILLEMIN Francis, Pr PHILIPPE Christophe
Tous les auteurs :
Frimat L, Philippe C, Maghakian MN, Jonveaux P, Hurault de Ligny B, Guillemin F, Kessler M
Lien Pubmed
Résumé
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 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.
Mots clés
Adolescent, Adult, Aged, Aged, 80 and over, Angiotensinogen, genetics, Child, Genotype, Glomerulonephritis, IGA, complications, Humans, Kidney Failure, Chronic, etiology, Longitudinal Studies, Male, Middle Aged, Peptidyl-Dipeptidase A, genetics, Polymorphism, Genetic, Predictive Value of Tests, Receptor, Angiotensin, Type 1, Receptor, Angiotensin, Type 2, Receptors, Angiotensin, genetics, Retrospective Studies, Survival Analysis
Référence
J. Am. Soc. Nephrol.. 2000 Nov;11(11):2062-7