OBJECTIVE: To determine the extent of variation in the gene for peroxisome proliferator activated receptor gamma (PPARgamma) in patients with morbid obesity. SUBJECTS: Two hundred morbidly obese patients who underwent gastric banding surgery and 192 healthy blood donors. Diabetics were excluded. EXPERIMENTAL: The frequency of the P115Q and P12A variants in the PPARgamma gene was determined. Single strand conformational polymorphism (SSCP) analysis was performed on all exons, exon/intron boundaries and part of the promoter of the PPARgamma gene on a sub-group of 67 morbid obese patients. RESULTS: None of the morbid patients or the blood donors were carriers of the P115Q mutation. The frequency of the P12A polymorphism did not differ significantly between morbid obese patients and controls and there was no statistically significant association between P12A and BMI. Male blood donors who were A12A homozygotes had statistically significant higher serum leptin concentrations (P = 0.001). Mutation screening revealed that one patient had a T -->G transversion at -208 in the promoter of PPARgamma-2, two had silent mutations, one a T-->C transition in the third base of codon 144 and the other a C-->T transition in codon 297. The fourth patient had a CGC-->TGC transition in codon 316 resulting in the replacement of an arginine with a cysteine. This mutation was not found in any other morbidly obese patient. CONCLUSION: Variation in the PPARgamma gene is unlikely to play a major role in the development of morbid obesity.
