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Impact of REV-ERB alpha gene polymorphisms on obesity phenotypes in adult and adolescent samples

International Journal of Obesity volume 37, pages 666–672 (2013)Cite this article

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Abstract

Background:

REV-ERBα has been shown to regulate adipogenesis and lipid metabolism as well as to link the circadian timing system to whole body metabolic homeostasis. We thus tested whether polymorphisms in REV-ERBα could be associated with metabolic phenotypes in human population samples.

Methods:

We analyzed the associations between 5 REV-ERBα polymorphisms and anthropometric (body weight, body mass index (BMI), waist and hip circumferences), biochemical (plasma lipid, glucose and insulin levels) and clinical (systolic and diastolic blood pressure) variables in three population-based studies (MONICA Lille n=1155 adults, MONA LISA Lille n=1170 adults and HELENA n=1155 adolescents). We assessed in vitro, the potential influence of one REV-ERBα polymorphism in transient transfection assays using two different cell lines.

Results:

We observed significant and consistent associations between the T minor allele of the REV-ERBα rs2071427 polymorphism (located in intron 1) and higher BMI (mean allele effect=+0.33 kg m−2) in the MONICA Lille (P=0.02), MONA LISA (P=0.02) and HELENA (P=0.03) studies. The odds ratios for obesity associated with this allele were 1.67 (1.00–2.79) (P=0.05) in MONICA Lille, 1.29 (1.01–1.65) (P=0.04) in MONA LISA Lille and the odds ratio for overweight was 1.48 (1.08–2.03) (P=0.01) in HELENA. In transfection experiments in human hepatocyte-derived cell lines, the REV-ERBα intron 1 directed the transcription of a luciferase reporter gene independently of the rs2071427 polymorphism.

Conclusion:

Our results suggest that the REV-ERBα rs2071427 polymorphism modulates body fat mass in both adult and young people.

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Acknowledgements

This study is part of the CRESCENDO (Consortium for Research into Nuclear Receptors in Development and Aging) consortium funded by the Commission′s Sixth Framework Program (integrated project LSHM-CT-2005-018652). The HELENA study received funding from the European Union′s Sixth RTD Framework Program (Contract FOOD-CT-2005-007034). The French arm of the WHO-MONICA population study was funded by grants from the Conseil Régional du Nord-Pas de Calais, the Caisse Primaire d′Assurance Maladie de Sélestat, the Association Régionale de Cardiologie d′Alsace, ONIVINS, Parke-Davis, the Mutuelle Générale de l′Education Nationale (MGEN), the Réseau National de Santé Publique, the Direction Générale de la Santé, the INSERM, the Institut Pasteur de Lille and the Unité d′Evaluation du Center Hospitalier et Universitaire de Lille. The MONA LISA Study was made possible by an unrestricted grant of Pfizer and by a grant from ANR (ANR-05-PNRA-018). The University of Nice Sophia-Antipolis and the CNRS are also acknowledged.

Author information

Authors and Affiliations

  1. INSERM, U744; Institut Pasteur de Lille; Univ Lille Nord de France; UDSL,

    L Goumidi, J Dumont, D Cottel, J Dallongeville, P Amouyel & A Meirhaeghe

  2. Institut Pasteur de Lille, Lille, France

    L Goumidi, J Dumont, D Cottel, J Dallongeville, P Amouyel & A Meirhaeghe

  3. Institut de Biologie Valrose, Université de Nice Sophia Antipolis, CNRS UMR7277, INSERM U1091, Nice, France

    A Grechez & F Delaunay

  4. Department of Social Medicine, Preventive Medicine and Nutrition Clinic, Faculty of Medicine, University of Crete, Heraklion, Greece

    A Kafatos

  5. Growth, Exercise, Nutrition and Development (GENUD) Research Group, School of Health Science (EUCS), University of Zaragoza, Zaragoza, Spain

    L A Moreno

  6. Department of Pediatrics, Medical Faculty, University of Pécs, Pécs, Hungary

    D Molnar

  7. Department of Nutrition and Dietetics, Harokopio University of Athens, Kallithea-Athens, Greece

    G Moschonis

  8. Inserm U995, Université Lille 2, Lille, France

    F Gottrand

  9. Department of Public Health, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium

    I Huybrechts

  10. Dietary Exposure Assessment Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, Lyon, France

    I Huybrechts

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  1. L Goumidi
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Correspondence to A Meirhaeghe.

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Goumidi, L., Grechez, A., Dumont, J. et al. Impact of REV-ERB alpha gene polymorphisms on obesity phenotypes in adult and adolescent samples. Int J Obes 37, 666–672 (2013). https://doi.org/10.1038/ijo.2012.117

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