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
CNRS-UMR-8090, Institute of Biology and Lille 2 University, Pasteur Institute, Lille, France.
Nat Genet. 2009 Jan;41(1):89-94. doi: 10.1038/ng.277. Epub 2008 Dec 7.
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.
在来自2151名非糖尿病法国受试者的全基因组关联（GWA）数据中，我们确定MTNR1B（编码褪黑素受体2（MT2））附近的rs1387153为空腹血糖（FPG；P = 1.3×10⁻⁷）的调节因子。在欧洲人群中，rs1387153的T等位基因与FPG升高（β = 0.06 mmol/l，P = 7.6×10⁻²⁹，N = 16,094）、2型糖尿病（T2D）风险（比值比（OR） = 1.15，95%置信区间 = 1.08 - 1.22，P = 6.3×10⁻⁵，病例数N = 6,332）以及9年内发生高血糖或糖尿病的风险（风险比（HR） = 1.20，95%置信区间 = 1.06 - 1.36，P = 0.005，新发病例数N = 515）相关。逆转录聚合酶链反应（RT-PCR）分析证实神经组织中存在MT2转录本，并显示MT2在人胰岛和β细胞中表达。我们的数据表明，通过褪黑素信号通路，昼夜节律调节与葡萄糖稳态之间可能存在联系。
