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

Peroxisome proliferator activated receptor-gamma (PPAR gamma) is a nuclear receptor that regulates adipocyte differentiation and possibly lipid metabo lism and insulin sensitivity. Therefore, PPAR gamma is a promising candidat e gene for several disorders including diabetes, obesity, and dyslipoprotei nemia. Screening for mutations in the entire coding region of the PPAR gamm a gene yielded a missense C --> G mutation at codon 12, resulting in the su bstitution of proline with alanine (Pro12Ala), The objective of our study w as to examine the relationship between this genetic variant and diabetes an d associated diseases in a large group of patients with type 1 (n = 522) an d type 2 (n = 503) diabetes, Allelic frequencies of the PPAR gamma(2) 12Ala allele were similar between patients with either type of diabetes and comp arable to that in healthy controls (n = 310). There was also no significant relationship between dyslipoproteinemia or obesity and the PPAR gamma(2) P ro12Ala genotype, Thus, our data, in this large and ethnically homogenous g roup of patients, do not support the hypothesis that this genetic variant i s strongly associated with diabetes, obesity, or dyslipidemia in patients w ith type 1 or type 2 diabetes mellitus, This genetic marker is therefore un likely to serve as a clinically useful predictor of these disorders in Cauc asian patients with diabetes mellitus. (C) 1999 Academic Press.