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

作者：Bouatia Naji Nabila; Bonnefond Amelie; Cavalcanti Proenca Christine; Sparso Thomas; Holmkvist Johan; Marchand Marion; Delplanque Jerome; Lobbens Stephane; Rocheleau Ghislain; Durand Emmanuelle; De Graeve Franck; Chevre Jean Claude; Borch Johnsen Knut; Hartikainen Anna Liisa; Ruokonen Aimo; Tichet Jean; Marre Michel; Weill Jacques; Heude Barbara; Tauber Maithe; Lemaire Katleen; Schuit Frans; Elliott Paul; Jorgensen Torben; Charpentier Guillaume; Hadjadj Samy

来源：Nature Genetics, 2009, 41(1): 89-94.

DOI：10.1038/ng.277

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.

• 出版日期2009-1