Molecular scanning of the human peroxisome proliferator activated receptor γ (hPPARγ) gene in diabetic Caucasians: Identification of a Pro12Ala PPARγ2 missense mutation

Abstract

Peroxisome proliferator activated receptor-gamma (PPARγ) is a nuclear receptor that regulates adipocyte differentiation, and possibly lipid metabolism and insulin sensitivity. As such, PPARγ is a promising candidate gene for several human disorders including obesity and type 2 diabetes mellitus. Screening for mutations in the entire coding region of the PPARγ gene (both γ1 and γ2 isoforms) was performed with DNA of 26 diabetic Caucasians with or without obesity. Two base substitutions were identified: a silent mutation at nucleotide 1431 (CAC(His)→CAT(His)) and a missense mutation (CCG(Pro)→GCG(Ala)) at codon 12 of PPARγ2. The allele frequency of the Pro12Ala PPARγ2 variant was 0.12 in Caucasian Americans, 0.10 in Mexican Americans, 0.08 in Samoans, 0.03 in African Americans, 0.02 in Nauruans, and 0.01 in Chinese. We conclude that the Pro12Ala PPARγ2 gene variant is present in diverse populations. Further studies of the Pro12Ala variant will determine its relevance to obesity, insulin resistance,and type 2 diabetes.