Abstract

Objective. Cross-sectional studies found less microalbuminuria in type 2 diabetic patients (T2D) with the Ala12 allele of the peroxisome proliferator-activated receptor-γ2 (PPAR-γ2) Pro12Ala polymorphism. We prospectively evaluated the association between Pro12Ala polymorphism (rs1801282) and new-onset microalbuminuria

Research Design and Methods. Pro12Ala polymorphism was genotyped by TaqMan-based assay in genomic DNA of 1119 consenting patients from BENEDICT, a prospective, randomized trial evaluating ACE inhibition effect on new-onset microalbuminuria (albuminuria 20-200 μg/min in at least 2 of 3 consecutive overnight urine collections in 2 consecutive visits) in hypertensive T2D with albuminuria <20 μg/min at inclusion.

Results. Baseline characteristics of Ala (Ala/Ala or Ala/Pro) carriers and Pro/Pro homozygotes were similar, with a non-significant trend to lower albuminuria (p=0.1107) in the 177 Ala carriers. Over a median (interquartile range) of 44.0 (17.1-51.9) months, 7 (4%) Ala carriers and 86 (9.1%) Pro/Pro homozygotes developed microalbuminuria [HR (95%CI)=0.45 (0.21-0.97), p=0.042]. Final albuminuria was significantly lower in Ala carriers (7.3±9.1 vs 10.5±24.9 μg/min, respectively), even after adjustment for baseline albuminuria (p=0.048). Baseline and follow-up blood pressure and metabolic control were similar in both groups. Incidence of microalbuminuria was significantly decreased by ACE vs non-ACE inhibitor therapy in Pro/Pro homozygotes [6.3% vs 11.9%, respectively, HR (95%CI)=0.46 (0.29-0.72), p<0.001].

Conclusions. In type 2 diabetes the Ala allele protects from worsening albuminuria and new-onset microalbuminuria, and ACE inhibition blunts the excess risk of microalbuminuria associated with the Pro/Pro genotype. Evaluating Pro12Ala polymorphism may help identifying patients at risk who may benefit the most of early renoprotective therapy.