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

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UNLABELLED: 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
Issue number3
Pages (from-to)347-51
Number of pages5
Publication statusPublished - Jul 2008

    Research areas

  • 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, Journal Article, Research Support, Non-U.S. Gov't

ID: 51533273