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Impact of the Peroxisome Proliferator Activated Receptor γ2 Pro12Ala polymorphism on adiposity, lipids and non-insulin-dependent diabetes mellitus

Abstract

OBJECTIVE: The Pro12Ala polymorphism of the Peroxisome Proliferator Activated Receptor γ2 (PPARγ2) 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 markers, 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 population study composed of 1195 subjects aged 35–64 y was randomly sampled from 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 interferences between medical treatment and biological variables. This resulted in a sample size of 839 subjects (421 men/418 women, age=49.4±8.1 y, body mass index (BMI)=25.7±4.4 kg/m2). To evaluate the role of the Pro12Ala polymorphism in the onset of NIDDM, we evaluated its distribution in 170 Caucasian NIDDM subjects from a clinical series (117 men/53 women, age=62.3±9.0 y, BMI=30.1±3.6 kg/m2).

MEASUREMENTS: The PPARγ2 Pro12Ala polymorphism genotyping was carried out with allele specific oligonucleotides hybridisation. Data were statistically 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. The 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 circumference (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 polymorphism was similar in NIDDM subjects (Ala allele frequency: 0.10) and in the WHO-MONICA population subjects.

CONCLUSION: Our results suggest that genetic variability of PPARγ2 affects body weight control and lipid homeostasis in humans and do not support a significant role for the PPARγ2 Pro12Ala polymorphism in the aetiology of NIDDM.

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Acknowledgements

We would like to thank Valérie Codron and Xavier Hermant for technical assistance. AM was supported by a grant from the Fondation pour la Recherche Médicale (FRM). This work was also supported by Ligand Pharmaceuticals, National Institutes of Health (USA) grant number HL3000686 to SD, NATO Collaborative Research grant 940514 to SD and JA. The WHO-MONICA population study developed in the north of France was supported by grants from the Conseil Régional du Nord-Pas de Calais, the Fondation pour la Recherche Médicale, ONIVINS, Parke-Davis Laboratory, the Mutuelle Générale de l'Education Nationale (MGEN), the Réseau National de Santé Publique, the Direction Générale de la Santé, the Institut National de la Santé Et de la Recherche Médicale (INSERM), the Institut Pasteur de Lille and the Unité d'Evaluation du Centre Hospitalier et Universitaire de Lille

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Correspondence to P Amouyel.

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Meirhaeghe, A., Fajas, L., Helbecque, N. et al. Impact of the Peroxisome Proliferator Activated Receptor γ2 Pro12Ala polymorphism on adiposity, lipids and non-insulin-dependent diabetes mellitus. Int J Obes 24, 195–199 (2000). https://doi.org/10.1038/sj.ijo.0801112

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