Pediatric primary nephrotic syndrome (PNS) is a chronic disease promoted by metabolic and immune dysfunctions. Peroxisome proliferator-activated receptor (PPAR) polymorphisms have been associated with a variety of metabolic and kidney disorders. We therefore hypothesized that PPAR polymorphisms might be involved in the pathophysiology of PNS. We compared the distributions of the PPAR- Pro12Ala and Val290Met, PPAR- coactivator- (PGC-1 ) Gly482Ser, and PPAR- Leu162Val single nucleotide polymorphisms (SNPs) between children with PNS and normal controls and analyzed their correlations with clinical and metabolic indicators and steroid responsiveness. There were no significant differences in distributions of any of the polymorphisms between PNS cases and controls. However, PNS patients with the PPAR- (Pro12Ala) PP genotype had significantly higher fasting serum insulin, IgA, and HOMA-IR levels and lower insulin sensitivity than did patients with PA and AA genotypes. Additionally, the PGC-1 (Gly482Ser) A allele was associated with lower CD8+ T-cell counts and higher triglyceride and complement C3 levels compared with the G allele. No polymorphisms were related to hormone sensitivity. These results suggest that the PPAR- (Pro12Ala) and PGC-1 (Gly482Ser) SNPs may influence insulin and triglyceride metabolism in children with PNS and may thus be relevant to the prognosis of this chronic condition. 1. Introduction Peroxisome proliferator-activated receptors (PPARs) are a group of ligand-activated nuclear transcription factors belonging to the type II nuclear receptor superfamily. Three PPAR subtypes, PPAR-α, PPAR-β, and PPAR-γ, have been identified in amphibians, rodents, and humans [1]. Recent studies have shown associations between PPAR gene polymorphisms and metabolic syndrome (MS) and the development of insulin resistance (IR). Gouda et al. [2] performed a meta-analysis of 32,849 patients with type II diabetes mellitus (T2DM) and 47,456 normal controls and found that the PPAR-γ (Pro12Ala) gene polymorphism was associated with IR and T2DM. In addition, Spars？ et al. [3] showed that the PPAR-α (Leu162Val) gene polymorphism was associated with obesity, T2DM, and abnormal lipid metabolism, while Andrulionytè et al. [4] found a link between the PPAR-γ coactivator-α (PGC-1α) Gly482Ser gene polymorphism and conversion from impaired glucose tolerance to T2DM. Children with primary nephrotic syndrome (PNS) suffer from metabolic abnormalities including glycolipid disorders, altered hemodynamics, and immune dysfunction, and previous studies have demonstrated that these
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