Leu162Val PPARα and Pro12Ala PPARγ2 were investigated for their individual and their interactive impact on MS and renal functionality (RF). 522 subjects were investigated for biochemical and anthropometric measurements. The diagnosis of MS was based on the IDF definition (2009). The HOMA 2 was used to determine HOMA-β, HOMA-S and HOMA-IR from FPG and FPI concentrations. RF was assessed by estimating the GFR. PCR-RFLP was performed for DNA genotyping. Allele frequencies were 0.845 for Pro and 0.155 for Ala, and were 0.915 for Leu and 0.085 for Val. We showed that carriers of the PPARα Val 162 allele had lower urea, UA and higher GFR compared to those homozygous for the Leu162 allele. Subjects carried by PPARγ2Ala allele had similar results. They also had reduced FPG, FPI and HOMA-IR, and elevated HOMA-β and HOMA-S compared to those homozygous for the Pro allele. Subjects were divided into 4 groups according to the combinations of genetic alleles of the 2 polymorphisms. Subjects carrying the Leu/Val with an Ala allele had lower FPG, PPI, HOMA-IR, urea, UA levels, higher HOMA-β, HOMA-S and GFR than different genotype combinations. Leu162Val PPARα and Pro12Ala PPARγ2 can interact with each other to modulate glucose and insulin homeostasis and expand their association with overall better RF. 1. Introduction Metabolic syndrome (MS) is a complex disorder characterized by the clustering of several metabolic diseases such as abdominal obesity, insulin resistance (IR), elevated plasma triglycerides level (TG), low high density lipoprotein cholesterol (cHDL), high blood pressure, and altered glucose homeostasis [1]. Environmental factors such as low physical activity and inappropriate dietary habits are strong determinants of the MS. In addition, genetic factors also contribute to the individual susceptibility to MS [2]. All components of the MS have individually been associated with the incidence and progression of chronic kidney diseases (CKDs). The mechanisms and impacts of hypertensive and diabetic injuries, the two major etiologies of CKD in the world, have been well studied and described [3–5]. Several observational studies found that individuals with the MS are at increased risk for presenting renal manifestations, namely, microalbuminuria and decreased glomerular filtration rate (GFR). In fact, epidemiological studies have linked MS with an increased risk for microalbuminuria, an early marker of glomerular injury and endothelial dysfunction [6–8]. Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors. They are ligand-dependent
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