Variation in the gene for human peroxisome proliferator activated receptorgamma (PPAR gamma) does not play a major role in the development of morbidobesity

OBJECTIVE: To determine the extent of variation in the gene for peroxisome proliferator activated receptor gamma (PPAR gamma) 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 PPAR gamm a gene was determined. Single strand conformational polymorphism (SSCP) ana lysis was performed on all exons, exon/intron boundaries and part of the pr omoter of the PPAR gamma gene on a sub-group of 67 morbid obese patients. RESULTS: None of the morbid patients or the blood donors were carriers of t he P115Q mutation. The frequency of the P12A polymorphism did not differ si gnificantly between morbid obese patients and controls and there was no sta tistically 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 h ad a T-->G transversion at - 208 in the promoter of PPAR gamma-2, two had s ilent 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-->T GC transition in codon 316 resulting in the replacement of an arginine with a cysteine. This mutation was not found in any other morbidly obese patien t. CONCLUSION: Variation in the PPAR gamma gene is unlikely to play a major ro le in the development of morbid obesity.