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


RESULTS
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.
Jorsal
A
A
Steno Diabetes Center, Niels Steensens Vej 2, 2820 Gentofte, Denmark. ajrs@steno.dk
Tarnow
L
L
Lajer
M
M
Ek
J
J
Hansen
T
T
Pedersen
O
O
Parving
H-H
HH
D000328:Adult; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D003928:Diabetic Nephropathies / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005919:Glomerular Filtration Rate / Q000235:genetics; D006801:Humans; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis
D047495:PPAR gamma