The PPAR gamma 2 Pro12Ala variant predicts ESRD and mortality in patients with type 1 diabetes and diabetic nephropathy

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A Jorsal, L Tarnow, M Lajer, J Ek, T Hansen, Oluf Pedersen, H-H Parving

The Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-gamma 2 gene is suggested to associate with diabetic nephropathy and cardiovascular disease in type 2 diabetes. The aim of this study was to investigate the polymorphism in relation to diabetic nephropathy, end-stage renal disease (ESRD), mortality and cardiovascular (CVD) events in type 1 diabetic patients. This prospective observational follow-up study included 415 type 1 diabetic patients with overt diabetic nephropathy (252 men; age 42.2+/-10.4 years [mean+/-SD], duration of diabetes 28.3+/-8.8 years, GFR 66+/-8.8 ml/min) and 428 patients with longstanding type 1 diabetes and persistent normoalbuminuria (230 men; age 45.4+/-11.6 years, duration of diabetes 27.8+/-10.1 years). Follow-up: 8.1 (0.0-12.8) years (median [range]). There where no significant differences between cases and controls in genotype (p=0.51) or allele frequencies (p=0.25). Cox regression analysis revealed a covariate-adjusted hazard ratio (HR) for all-cause mortality in patients with the Ala/Ala genotype of 2.44 (1.23-4.84). The Pro12Ala polymorphism did not predict CVD events. However, the Ala/Ala genotype predicts ESRD (covariate-adjusted HR 2.60 (1.11-6.07)). Furthermore, Carriers of the Ala-allele had a higher rate of decline in GFR (p=0.040). In conclusion, the Pro12Ala polymorphism is not associated with type 1 diabetic nephropathy. The Ala-allele is associated with enhanced decline in GFR and predicts ESRD and all-cause mortality in patients with nephropathy.
Original languageEnglish
JournalMolecular Genetics and Metabolism
Volume94
Issue number3
Pages (from-to)347-51
Number of pages4
ISSN1096-7192
DOIs
Publication statusPublished - 2008

Bibliographical note

Keywords: Adult; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Follow-Up Studies; Gene Frequency; Genetic Predisposition to Disease; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; PPAR gamma; Polymorphism, Single Nucleotide; Prognosis; Prospective Studies; Survival Analysis

ID: 10027333