The Rate of Decline of Glomerular Filtration Rate May Not Be Associated with Polymorphism of the PPAR 2 Gene in Patients with Type 1 Diabetes and Nephropathy
The aim of the study was to investigate whether a Pro12Ala polymorphism in the peroxisome proliferator-activated receptor gamma 2 (PPARγ2) gene is associated with the progress of diabetic nephropathy in patients with type 1 diabetes. 197 Caucasian patients with type 1 diabetes and ethnically matched 151 normal healthy controls were genotyped for this polymorphism. Results showed that there were no significant differences in the frequencies of the genotypes and alleles of the polymorphism between groups. Multiple regression analysis in 77 patients demonstrated that the rate of decline in renal function in terms of glomerular filtration rate was significantly correlated to the baseline level of cholesterol ( ), mean diastolic blood pressure during follow-up period ( ), and baseline level of HbA1c ( ) adjusting for the effect of diabetes duration and gender, but no significant association was found between the polymorphism and the progression of diabetic nephropathy in our studied population. In summary, our results show that the PPARγ2 polymorphism is unlikely to be associated with the development and progression of the diabetic nephropathy in patients with type 1 diabetes. Further studies in different populations may be warranted to confirm our findings as the sample size in our study was relatively small. 1. Introduction Peroxisome proliferation-activated receptor γ (PPARγ) is a nuclear receptor which is an important regulator of adipocyte differentiation and a modulator of intracellular insulin-signalling events. There are two isoforms in PPARγ: PPARγ1 and PPARγ2. PPARγ2 is a ligand-activated transcription factor and a member of the steroid receptor superfamily. It is expressed in vascular smooth muscle cells, mesangial cells, and macrophages [1], which has been shown to be involved in lipid and glucose metabolism, fatty acid transport, and cell differentiation [2]. It is also highly expressed in renal epithelial cells [3, 4]. In addition, PPARγ activation abrogated gene expression of metalloproteinase 9 (MMP-9) in murine macrophages [5, 6] and secretion of MMP-9 in the THP-1 human monocytic cell line [7]. These findings suggest that PPARγ may play diverse roles in cell growth, differentiation, and extracellular matrix accumulation. The thiazolidinediones act as PPARγ ligand [8, 9] and have been reported to decrease albuminuria in patients with early diabetic nephropathy [10]. This indicates a possible role of PPARγ in the development of the diabetes-associated microvascular phenotype. Ala12Prol substitution in exon B of the PPARγ2 gene is within the
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