A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk Academic Article uri icon

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abstract

  • In genome-wide association (GWA) data from 2,151 nondiabetic French subjects, we identified rs1387153, near MTNR1B (which encodes the melatonin receptor 2 (MT2)), as a modulator of fasting plasma glucose (FPG; P = 1.3 x 10(-7)). In European populations, the rs1387153 T allele is associated with increased FPG (beta = 0.06 mmol/l, P = 7.6 x 10(-29), N = 16,094), type 2 diabetes (T2D) risk (odds ratio (OR) = 1.15, 95% CI = 1.08-1.22, P = 6.3 x 10(-5), cases N = 6,332) and risk of developing hyperglycemia or diabetes over a 9-year period (hazard ratio (HR) = 1.20, 95% CI = 1.06-1.36, P = 0.005, incident cases N = 515). RT-PCR analyses confirm the presence of MT2 transcripts in neural tissues and show MT2 expression in human pancreatic islets and beta cells. Our data suggest a possible link between circadian rhythm regulation and glucose homeostasis through the melatonin signaling pathway.

authors

  • Bouatia-Naji, Nabila
  • Bonnefond, Amélie
  • Cavalcanti-Proença, Christine
  • Sparsø, Thomas
  • Holmkvist, Johan
  • Marchand, Marion
  • Delplanque, Jérôme
  • Lobbens, Stéphane
  • Rocheleau, Ghislain
  • Durand, Emmanuelle
  • De Graeve, Franck
  • Chèvre, Jean-Claude
  • Borch-Johnsen, Knut
  • Hartikainen, Anna-Liisa
  • Ruokonen, Aimo
  • Tichet, Jean
  • Marre, Michel
  • Weill, Jacques
  • Heude, Barbara
  • Tauber, Maithé
  • Lemaire, Katleen
  • Schuit, Frans
  • Elliott, Paul
  • Jørgensen, Torben
  • Charpentier, Guillaume
  • Hadjadj, Samy
  • Cauchi, Stéphane
  • Vaxillaire, Martine
  • Sladek, Robert
  • Visvikis-Siest, Sophie
  • Balkau, Beverley
  • Lévy-Marchal, Claire
  • Pattou, François
  • Meyre, David Jean-Claude
  • Blakemore, Alexandra IF
  • Jarvelin, Marjo-Riita
  • Walley, Andrew J
  • Hansen, Torben
  • Dina, Christian
  • Pedersen, Oluf
  • Froguel, Philippe

publication date

  • January 2009

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