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

• DOI: 10.1038/ng.277
• Publication Date: 2008-12-07T19:17:21Z
• Authors: Nabila Bouatia-Naji; Amélie Bonnefond; Christine Cavalca...; Thomas Sparsø; Johan Holmkvist; Marion Marchand; Jérôme Delplanque; Stéphane Lobbens; Ghislain Rocheleau; Emmanuelle Durand; Franck De Graeve; Jean-Claude Chèvre; Knut Borch-Johnsen; Anna-Liisa Hartik...; Aimo Ruokonen; Jean Tichet; Michel Marre; Jacques Weill; Barbara Heude; Maithé Tauber; Katleen Lemaire; Frans Schuit; Paul Elliott; Torben Jørgensen; Guillaume Charpen...; Samy Hadjadj; Stéphane Cauchi; Martine Vaxillaire; Robert Sladek; Sophie Visvikis-S...; Beverley Balkau; Claire Lévy-Marchal; François Pattou; David Meyre; Alexandra I F Bla...; Marjo-Riita Jarvelin; Andrew J Walley; Torben Hansen; Christian Dina; Oluf Pedersen; Philippe Froguel
• Keywords: Pancreatic Islets

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.