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

Nabila Bouatia-Naji, Amélie Bonnefond, Christine Cavalcanti-Proença, 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 Hartikainen, Aimo Ruokonen, Jean Tichet, Michel Marre, Jacques Weill, Barbara Heude, Maithé TauberKatleen Lemaire, Frans Schuit, Paul Elliott, Torben Jørgensen, Guillaume Charpentier, Samy Hadjadj, Stéphane Cauchi, Martine Vaxillaire, Robert Sladek, Sophie Visvikis-Siest, Beverley Balkau, Claire Lévy-Marchal, François Pattou, David Meyre, Alexandra I.F. Blakemore, Marjo Riita Jarvelin, Andrew J. Walley, Torben Hansen, Christian Dina, Oluf Pedersen, Philippe Froguel*

*Corresponding author af dette arbejde

    Publikation: Bidrag til tidsskriftArtikelForskningpeer review

    Abstrakt

    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 × 10-7). In European populations, the rs1387153 T allele is associated with increased FPG (β = 0.06 mmol/l, P = 7.6 × 10 -29, N = 16,094), type 2 diabetes (T2D) risk (odds ratio (OR) = 1.15, 95% CI = 1.08-1.22, P = 6.3 × 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.

    OriginalsprogEngelsk
    Sider (fra-til)89-94
    Antal sider6
    TidsskriftNature Genetics
    Vol/bind41
    Udgave nummer1
    DOI
    StatusUdgivet - jan. 2009

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