A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk.
Bouatia-Naji N,
Bonnefond A,
Cavalcanti-Proença C,
Sparsø T,
Holmkvist J,
Marchand M,
Delplanque J,
Lobbens S,
Rocheleau G,
Durand E,
De Graeve F,
Chèvre JC,
Borch-Johnsen K,
Hartikainen AL,
Ruokonen A,
Tichet J,
Marre M,
Weill J,
Heude B,
Tauber M,
Lemaire K,
Schuit F,
Elliott P,
Jørgensen T,
Charpentier G,
Hadjadj S,
Cauchi S,
Vaxillaire M,
Sladek R,
Visvikis-Siest S,
Balkau B,
Lévy-Marchal C,
Pattou F,
Meyre D,
Blakemore AI,
Jarvelin MR,
Walley AJ,
Hansen T,
Dina C,
Pedersen O,
Froguel P.
CNRS-UMR-8090, Institute of Biology and Lille 2 University, Pasteur Institute, Lille, France.
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.
PMID: 19060909 [PubMed - indexed for MEDLINE]