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

L. Goumidi, A. Grechez, J. Dumont, D. Cottel, A. Kafatos, L. A. Moreno, D. Molnar, G. Moschonis, F. Gottrand, I. Huybrechts, J. Dallongeville, P. Amouyel, F. Delaunay, A. Meirhaeghe

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background:REV-ERB 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-ERB could be associated with metabolic phenotypes in human population samples.Methods:We analyzed the associations between 5 REV-ERB 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-ERB 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-ERB 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-ERB intron 1 directed the transcription of a luciferase reporter gene independently of the rs2071427 polymorphism.Conclusion:Our results suggest that the REV-ERB rs2071427 polymorphism modulates body fat mass in both adult and young people.

Original languageEnglish
Pages (from-to)666-672
Number of pages7
JournalInternational Journal of Obesity
Volume37
Issue number5
DOIs
Publication statusPublished - May 1 2013

    Fingerprint

Keywords

  • BMI
  • NR1D1
  • REV-ERBa
  • adult and young population
  • fat mass
  • polymorphism

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Goumidi, L., Grechez, A., Dumont, J., Cottel, D., Kafatos, A., Moreno, L. A., Molnar, D., Moschonis, G., Gottrand, F., Huybrechts, I., Dallongeville, J., Amouyel, P., Delaunay, F., & Meirhaeghe, A. (2013). Impact of REV-ERB alpha gene polymorphisms on obesity phenotypes in adult and adolescent samples. International Journal of Obesity, 37(5), 666-672. https://doi.org/10.1038/ijo.2012.117