The Pro12Ala Variant of thePPARGGene Is a Risk Factor for Peroxisome Proliferator-Activated Receptor-γ/α Agonist-Induced Edema in Type 2 Diabetic Patients

Abstract

A population-attributable risk of approximately 50% for the Pro12Pro genotype indicates that testing for the Pro12Ala of the PPARG gene in addition to the already identified clinical risk factors may become a useful tool to further reduce the risk of PPARgamma agonist-induced fluid retention and edema in patients with type 2 diabetes.

Retinoid X Receptor Heterodimer Variants and Cardiovascular Risk Factors

“…With regard to the response to TZD treatment, subjects with the Ala12 allele showed a better response to therapy than those with Pro12 homozygotes in one study 89) , and no difference was observed between the two genotypes in another 90) ; however, the Ala12 allele was the most important risk factor for TZD-induced edema 91) . As PPAR plays an important role in osteocyte differentiation 66,67) , it is possible to speculate on its association with bone metabolism.…”

A Pilot Study Suggests that the G/G Genotype of Resistin Single Nucleotide Polymorphism at -420 May Be an Independent Predictor of a Reduction in Fasting Plasma Glucose and Insulin Resistance by Pioglitazone in Type 2 Diabetes

“…it has been recognized that some type 2 diabetic patients respond to tzds with the improved hyperglycemia (responders), whereas others do not (non-responders) [9]. Single nucleotide polymorphism (SnP) of genes contributing to body weight gain or edema by tzds has been reported [10,11]. however, genetic factors affecting improvement of hyperglycemia remain to be determined.…”

Diabetes Type 1 and 2: What is Behind a Classification?

“…It is a member of the nuclear hormone receptor family involved in adipocyte differentiation and gene expression regulation, and it is a transcriptional factor involved in adipogenesis and regulation of adipocyte gene expression. PPAR plays a role in insulin signaling, insulin resistance and the development of type 2 diabetes mellitus (Chawla et al, 1994;Auwerx, 1999;Zhang et al, 2007) A splice variant of this gene contains a common amino acid polymorphism, Pro12Ala (carrier frequencies 8-20%, depending on the population) that, depending on the cell lines, reduces the ligand-induced activity of the PPAR protein by 30-50% (Altshuler et al, 2000;Deeb et al, 1998;Hansen et al, 2006). This missense mutation (involving a C to G substitution at nucleotide 34) results in the exchange of a proline for an alanine in position 12 of the PPARγ2 protein (Yen et al, 1997).…”