title: Impact of REV-ERB alpha gene polymorphisms on obesity phenotypes in adult and adolescent samples.
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.
  
  
  CONCLUSIONS
  Our results suggest that the REV-ERBα rs2071427 polymorphism modulates body fat mass in both adult and young people.
authors: INSERM, U744, Institut Pasteur de Lille, Univ Lille Nord de France, UDSL, Lille, France.
authors: L
authors: L
authors: Goumidi
authors: A
authors: A
authors: Grechez
authors: J
authors: J
authors: Dumont
authors: D
authors: D
authors: Cottel
authors: A
authors: A
authors: Kafatos
authors: L A
authors: LA
authors: Moreno
authors: D
authors: D
authors: Molnar
authors: G
authors: G
authors: Moschonis
authors: F
authors: F
authors: Gottrand
authors: I
authors: I
authors: Huybrechts
authors: J
authors: J
authors: Dallongeville
authors: P
authors: P
authors: Amouyel
authors: F
authors: F
authors: Delaunay
authors: A
authors: A
authors: Meirhaeghe
mesh_terms: D000293:Adolescent; D000328:Adult; D000886:Anthropometry; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002648:Child; D002940:Circadian Rhythm; D005060:Europe / Q000453:epidemiology; D005260:Female; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; C064353:NR1D1 protein, human; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1