Pro12Ala mutation in the peroxisome proliferator-activated receptor gamma 2 (PPAR gamma 2) and severe obesity: a case-control study

OBJECTIVE: To explore the association of the Pro12Ala mutation in the perox isome proliferator-activated receptor gamma 2 with severe obesity and the f eatures of the metabolic syndrome in a population-based sample of Caucasian s. PARTICIPANTS AND METHODS: The study is based on a case-control design: 95 n on-diabetic severely obese (body mass index, BMI > 35 kg/m(2)) cases and 28 0 normal weight (BMI < 25 kg/m(2)), age- and sex-matched controls selected from the same population were studied. Height, weight, waist circumference, as well as blood pressure were measured according to a standard protocol. BMI at age 25 y was calculated on the basis of current height and reported weight at age 25 y Biochemical measurements included fasting glucose, trigl ycerides. high-density lipoprotein cholesterol and insulin. DNA analysis wa s conducted by PCR and gel electrophoresis. RESULTS: Age and gender distribution were similar in obese and normal weigh t participants. The percentage of people with the Pro12Ala mutation was not significantly different in obese or normal weight participants (20% and ;1 5%, respectively; P = 0.32), Conversely, in obese participants with obesity starling in early adulthood lie with BMI at age 25 above 26.9 kg/m(2) whic h represents the median of the whole obese group), the Pro12Ala mutation wa s observed significantly more frequently than in the normal weight controls (29% vs 15%; chi square = 4.5, P < 0.05; odds ratio 2.4; 95% CI 1.03-5.36) . No association of the Pro12Ala variant with any of the component of the m etabolic syndrome measured in the study was observed in either obese, juven ile obese or normal weight participants. CONCLUSIONS: Results of this study indicate that the Pro12Ala mutation does not play a major role as a determinant of severe obesity and/or features o f the metabolic syndrome in the general population. However, this mutation may be of greater importance as a contributor to early onset obesity.