PPAR 2 P12A polymorphism and albuminuria in patients with type 2 diabetes: a meta-analysis of case-control studies

Abstract

Insulin resistance has a role in diabetic nephropathy. The A12 variant of the PPARγ2 P121A polymorphism has been firmly associated with reduced risk of insulin resistance, while its role on the risk of albuminuria in patients with type 2 diabetes is uncertain. This study investigated whether the PPARγ2 P12A polymorphism modulates the risk of albuminuria in these patients. We tested the association between the A12 variant and albuminuria in three new case-control studies in diabetic patients from Italy (n = 841, n = 623 and n = 714 patients, respectively) and then performed a meta-analysis of all studies available to date. The nine studies we meta-analysed (six previously published and three presented here) comprised a total of 2376 cases and 4188 controls. In none of the three new studies was a significant association observed with odds ratio (OR) [95% confidence intervals (95% CI)] being 1.115, 0.799 and 0.849 (P = 0.603, 0.358 and 0.518, respectively). At meta-analysis, the overall OR (95% CI) for association between A12 and albuminuria was 0.694 (0.528-0.912). A significant heterogeneity of the genetic effect was observed (P = 0.026), which was totally explained by the different method of urine collection and albuminuria definition utilized across the studies. In fact, most of the effect was observed in the four studies determining albumin excretion rate rather than in those using albumin concentration in a single spot (OR, 95% CI: 0.529, 0.397-0.706, P = 0.0000164 and 0.919, 0.733-1.153, P = 0.47, respectively). The present study shows that the PPARγ2 Ala12 variant is significantly associated with a reduced risk of albuminuria among patients with type 2 diabetes.