Pro12Ala polymorphism of the PPARgamma2 locus modulates the relationship between energy intake and body weight in type 2 diabetic patients

OBJECTIVE: We explore the relationship among BMI, habitual diet, and the Pro12Ala polymorphism in the peroxisome proliferator-activated receptor (PPAR)gamma2. RESEARCH DESIGN AND METHODS: The Pro12Ala variant was characterized in 343 unrelated type 2 diabetic patients who were consecutively seen at the outpatient clinic of a health district of the province of Naples. Anthropometric and laboratory parameters were measured; habitual diet was assessed by a validated semiquantitative food frequency questionnaire. RESULTS: The overall frequency of Ala12 was 12% (n = 42). BMI was significantly higher in Ala carriers than non-Ala carriers, whereas total daily energy intake or macronutrient composition of the diet were similar in the two groups. For further analysis, participants were stratified according to genotype and sex-specific quartiles of energy intake. BMI increased in both genotype groups with increasing energy intake (P 0.10) in the lower quartile of energy intake but significantly higher in Ala carriers in the upper quartile (36.0 vs. 32.1 kg/m2, P < 0.001). Average daily energy intake and diet composition were comparable within each quartile for carriers or noncarriers of the Ala allele. Relative to the noncarriers, Ala carriers had a significantly lower energy intake per kilogram body weight, thus suggesting that the Ala allele is associated with a higher food efficiency. The confounding role of medications, glucose control, and physical exercise was ruled out. CONCLUSIONS: This study provides evidence of a differential susceptibility to fat accumulation, and, hence, weight gain, in response to habitual high energy intake for Ala carriers compared with Pro/Pro homozygotes. PMID: 17259473 [PubMed - indexed for MEDLINE