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

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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 Tauber & 21 others Katleen 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

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.
Original languageEnglish
JournalNature Genetics
Volume41
Issue number1
Pages (from-to)89-94
Number of pages5
ISSN1061-4036
DOIs
Publication statusPublished - 2009

Bibliographical note

Keywords: Adaptor Proteins, Signal Transducing; Adolescent; Adult; Blood Glucose; Child; Chromosomes, Human, Pair 11; Cohort Studies; Diabetes Mellitus, Type 2; Fasting; Gene Expression Profiling; Gene Expression Regulation; Genetic Predisposition to Disease; Genome-Wide Association Study; Glucokinase; Humans; Insulin Resistance; Islets of Langerhans; Meta-Analysis as Topic; Middle Aged; Polymorphism, Single Nucleotide; RNA, Messenger; Receptor, Melatonin, MT2; Receptors, Melatonin; Reproducibility of Results

ID: 11550950