Peroxisome proliferator-activated receptor γ polymorphism Pro12Ala is associated with nephropathy in type 2 diabetes

Aim: One putative determinant of diabetic nephropathy is the Pro12Ala (P12A) polymorphism in the gene encoding peroxisome proliferator-activated receptor gamma (PPAR gamma). Previous research has found a protective' role for the A12 allele in association with type 2 diabetes, atherosclerosis, and measures of kidney damage. The objective of this study was to investigate a possible role for the P12A PPAR gamma gene polymorphism with diabetic nephropathy in an isolated aboriginal Canadian population at high risk for renal disease. Methods: The P12A PPAR gamma gene polymorphism was genotyped in 159 subjects (62 men and 97 women) of Oji-Cree descent. Participants were selected from a communitywide survey, which included diabetic nephropathy assessment by albumin/creatinine (A/C) ratio measurement. Genetic associations were tested by multivariate regression analysis, using a forward stepwise modeling approach. Results: PPAR gamma A12 allele carriers had reduced prevalence of microalbuminuria with a similar to 1.5-fold reduction in A/C ratio. Both PPARG P12A genotype [odds ratio (OR)=0.25, 95% confidence interval (95% CI)=0.076-0.85, P=.026] and systolic blood pressure (OR=1.69, 95% CI=1.15-2.48, P=.0075) were associated with microalbuminuria. Conclusions: The genetic influence of PPARG P12A genotype is modest and is overshadowed by duration of diabetes and systolic blood pressure as the major risk factors for diabetic nephropathy in the Oji-Cree population. The observed genetic association with diabetic nephropathy, however, confirms earlier findings, highlighting the importance of this polymorphism. (c) 2007 Elsevier Inc. All rights reserved.