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

• Published in: Nature genetics Vol. 41; no. 1; pp. 89 - 94
• Main 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, Blakemore, Alexandra I F, Jarvelin, Marjo-Riita, Walley, Andrew J, Hansen, Torben, Dina, Christian, Pedersen, Oluf, Froguel, Philippe
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2009; Nature Publishing Group
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adolescent; Adult; Agriculture; Animal Genetics and Genomics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Blood Glucose - genetics; Cancer Research; Child; Chromosomes, Human, Pair 11 - genetics; Cohort Studies; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - enzymology; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fasting - blood; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Gene Function; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Glucokinase - genetics; Glucose; Health risks; Human Genetics; Humans; Hyperglycemia; Insulin Resistance - genetics; Islets of Langerhans - metabolism; Islets of Langerhans - pathology; letter; Medical sciences; Meta-Analysis as Topic; Middle Aged; Mortality; Polymorphism, Single Nucleotide - genetics; Receptor, Melatonin, MT2 - genetics; Receptor, Melatonin, MT2 - metabolism; Receptors, Melatonin - genetics; Receptors, Melatonin - metabolism; Reproducibility of Results; Risk factors; RNA, Messenger - genetics; RNA, Messenger - metabolism; Statistical analysis; Endocrinopathy; Type 2 diabetes; Variant; Plasma; Metabolic diseases; Risk; Glucose
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.277

Philippe Froguel and colleagues report an association of variants near the gene encoding melatonin receptor 2 with fasting glucose levels and risk of type 2 diabetes. The association suggests a possible link between circadian rhythm and glucose homeostasis. 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.