title: A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk.
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.affiliation: CNRS-UMR-8090, Institute of Biology and Lille 2 University, Pasteur Institute, Lille, France.
authors.forename: Nabila
authors.initials: N
authors.lastname: Bouatia-Naji
authors.forename: Amélie
authors.initials: A
authors.lastname: Bonnefond
authors.forename: Christine
authors.initials: C
authors.lastname: Cavalcanti-Proença
authors.forename: Thomas
authors.initials: T
authors.lastname: Sparsø
authors.forename: Johan
authors.initials: J
authors.lastname: Holmkvist
authors.forename: Marion
authors.initials: M
authors.lastname: Marchand
authors.forename: Jérôme
authors.initials: J
authors.lastname: Delplanque
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lobbens
authors.forename: Ghislain
authors.initials: G
authors.lastname: Rocheleau
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Durand
authors.forename: Franck
authors.initials: F
authors.lastname: De Graeve
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Chèvre
authors.forename: Knut
authors.initials: K
authors.lastname: Borch-Johnsen
authors.forename: Anna-Liisa
authors.initials: AL
authors.lastname: Hartikainen
authors.forename: Aimo
authors.initials: A
authors.lastname: Ruokonen
authors.forename: Jean
authors.initials: J
authors.lastname: Tichet
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.forename: Jacques
authors.initials: J
authors.lastname: Weill
authors.forename: Barbara
authors.initials: B
authors.lastname: Heude
authors.forename: Maithé
authors.initials: M
authors.lastname: Tauber
authors.forename: Katleen
authors.initials: K
authors.lastname: Lemaire
authors.forename: Frans
authors.initials: F
authors.lastname: Schuit
authors.forename: Paul
authors.initials: P
authors.lastname: Elliott
authors.forename: Torben
authors.initials: T
authors.lastname: Jørgensen
authors.forename: Guillaume
authors.initials: G
authors.lastname: Charpentier
authors.forename: Samy
authors.initials: S
authors.lastname: Hadjadj
authors.forename: Stéphane
authors.initials: S
authors.lastname: Cauchi
authors.forename: Martine
authors.initials: M
authors.lastname: Vaxillaire
authors.forename: Robert
authors.initials: R
authors.lastname: Sladek
authors.forename: Sophie
authors.initials: S
authors.lastname: Visvikis-Siest
authors.forename: Beverley
authors.initials: B
authors.lastname: Balkau
authors.forename: Claire
authors.initials: C
authors.lastname: Lévy-Marchal
authors.forename: François
authors.initials: F
authors.lastname: Pattou
authors.forename: David
authors.initials: D
authors.lastname: Meyre
authors.forename: Alexandra I F
authors.initials: AI
authors.lastname: Blakemore
authors.forename: Marjo-Riita
authors.initials: MR
authors.lastname: Jarvelin
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Walley
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.forename: Christian
authors.initials: C
authors.lastname: Dina
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000235:genetics*; D002648:Child; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000201:enzymology / Q000235:genetics*; D005215:Fasting / Q000097:blood*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005941:Glucokinase / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044123:Receptor, Melatonin, MT2 / Q000235:genetics* / Q000378:metabolism; D044094:Receptors, Melatonin / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001786:Blood Glucose; C485100:GCKR protein, human; D012333:RNA, Messenger; D044123:Receptor, Melatonin, MT2; D044094:Receptors, Melatonin; D005941:Glucokinase