Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD) worldwide, and it is estimated that 20% of T2D patients reach ESRD during their lifetime . The pathogenesis of DN has many genetic and environmental factors contributing to its development and progression. The risk of developing DN has been linked to different chromosomes, including chromosome 3, to which the peroxisome proliferators-activated receptor (PPAR) gene has been mapped, particularly to the PPAR gamma (PPARG) nuclear receptor, which is mainly expressed in adipose tissue but is also found in pancreatic beta cells, vascular endothelium, and macrophage [2, 3].
PPAR-γ2 is a nuclear receptor that serves important roles in intermediate metabolism. The PPARG gene is located on chromosome 3p . The Pro12Ala polymorphism of the PPARG gene, a Pro-to-Ala exchange that results in the substitution of proline with alanine at codon 12, was associated with reductions in both DNA binding and transcriptional activity in vitro, and Ala12 carriers showed significant improvement in insulin sensitivity [4, 5]. The Pro12Ala polymorphism in the PPARG gene is suggested to be associated with DN. As we all kwon, many epidemiologic studies investigated the potential association of PPARG gene polymorphisms with susceptibility to DN. However, these studies have reported inconclusive results.
One putative genetic determinant of DN is the Pro12Ala polymorphism in the gene encoding PPARg. PPARg, a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors, plays a key role in regulating the expression of numerous genes involved in lipid metabolism, metabolic syndrome, inflammation, and atherosclerosis [6, 7]. The P12A single-nucleotide polymorphism (SNP) located in the adipocyte-specific PPARg2 isoform has been associated with lower nephropathy in T2D [8, 9]. The underlying molecular mechanism of this polymorphism appears to be, in vitro, a moderate reduction in DNA-binding activity and reduced transcriptional activity [4, 10]. In the present study, we examined the relationship between PPAR-γ2 gene polymorphisms and the risk of T2D DN.