학술논문
A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk.
Document Type
Article
Author
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
Source
Subject
*TYPE 2 diabetes risk factors
*HYPERGLYCEMIA
*MELATONIN
*CIRCADIAN rhythms
*GLUCOSE
*HOMEOSTASIS
*ISLANDS of Langerhans
*DISEASE risk factors
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Language
ISSN
1061-4036
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 × 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. [ABSTRACT FROM AUTHOR]