Peroxisome proliferator activated receptor-gamma (PPARγ) is a nuclear receptor that regulates adipocyte differentiation and possibly lipid metabolism and insulin sensitivity. Therefore,PPARγis a promising candidate gene for several disorders including diabetes, obesity, and dyslipoproteinemia. Screening for mutations in the entire coding region of thePPARγgene yielded a missense C → G mutation at codon 12, resulting in the substitution of proline with alanine (Pro12Ala). The objective of our study was to examine the relationship between this genetic variant and diabetes and associated diseases in a large group of patients with type 1 (n= 522) and type 2 (n= 503) diabetes. Allelic frequencies of thePPARγ₂12Ala allele were similar between patients with either type of diabetes and comparable to that in healthy controls (n= 310). There was also no significant relationship between dyslipoproteinemia or obesity and thePPARγ₂Pro12Ala genotype. Thus, our data, in this large and ethnically homogenous group of patients, do not support the hypothesis that this genetic variant is strongly associated with diabetes, obesity, or dyslipidemia in patients with type 1 or type 2 diabetes mellitus. This genetic marker is therefore unlikely to serve as a clinically useful predictor of these disorders in Caucasian patients with diabetes mellitus.