Pro12Ala missense mutation of the peroxisome proliferator activated receptor γ and diabetes mellitus

Peroxisome proliferator activated receptor-gamma (PPAR gamma) is a nuclear receptor that regulates adipocyte differentiation and possibly lipid metabolism and insulin sensitivity. Therefore, PPAR gamma is a promising candidate gene for several disorders including diabetes, obesity, and dyslipoproteinemia. Screening for mutations in the entire coding region of the PPAR gamma gene 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 the PPAR gamma(2) 12Ala 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 the PPAR gamma(2) Pro12Ala 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. (C) 1999 Academic Press.