Impact of the Peroxisome Proliferator Activated Receptor gamma 2 Pro12Ala polymorphism on adiposity, lipids and non-insulin-dependent diabetes mellitus

OBJECTIVE: The Pro12Ala polymorphism of the Peroxisome Proliferator Activat ed Receptor gamma 2 (PPAR gamma 2) gene has been inconsistently associated with body mass index variations and non-insulin-dependent diabetes mellitus (NIDDM). We investigated the impact of this polymorphism on obesity marker s, lipid and glucose variables in a sample of French subjects and evaluated its possible role in the onset of NIDDM. DESIGN AND SUBJECTS: Within the framework of the WHO-MONICA project, a popu lation study composed of 1195 subjects aged 35-64y was randomly sampled fro m the electoral rolls of the urban community of Lille, in northern France. Subjects receiving medical treatment for hypercholesterolemia, hypertension or diabetes mellitus were excluded for the analyses, to avoid any interfer ences between medical treatment and biological variables. This resulted in a sample size of 839 subjects (421 men/418 women, age = 49.4 +/- 8.1y, body mass index (BMI) = 25.7 +/- 4.4 kg/m(2)). To evaluate the role of the Pro1 2Ala polymorphism in the onset of NIDDM, we evaluated its distribution in 1 70 Caucasian NIDDM subjects from a clinical series (117 men/53 women, age = 62.3 +/- 9.0y, BMI = 30.1 +/- 3.6 kg/m(2)). MEASUREMENTS: The PPAR gamma 2 Pro12Ala polymorphism genotyping was carried out with allele specific oligonucleotides hybridisation. Data were statist ically analysed for association with various obesity markers (body weight ( BW), BMI, waist-to-hip ratio (WHR), plasma leptin concentrations, lipid and glucose variables. RESULTS: In the WHO-MONICA population, the Ala allele frequency was 0.11. T he presence of the Ala allele was significantly associated with higher body weight (P = 0.002), BMI (P = 0.02), height (P = 0.02) and waist circumfere nce (P = 0.04). Increased plasma concentrations of total cholesterol (P = 0 .01), LDL-cholesterol (P = 0.004) and apolipoprotein B (P = 0.01) were also detected in Ala allele bearers. The distribution of the Pro12Ala polymorph ism was similar in NIDDM subjects (Ala allele frequency: 0.10) and in the W HO-MONICA population subjects. CONCLUSION: Our results suggest that genetic variability of PPAR gamma 2 af fects body weight control and lipid homeostasis in humans and do not suppor t a significant role for the PPARyZ Pro12Ala polymorphism in the aetiology of NIDDM.