A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk
A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk
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DOI：
10.1038/ng.277
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发表时间：
2009-01-01
期刊：
影响因子：
30.8
通讯作者：
Froguel, Philippe
中科院分区：
文献类型：
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作者：
Bouatia-Naji, Nabila;Bonnefond, Amelie;Froguel, Philippe
在来自2,151名法国非糖尿病受试者的全基因组关联（GWA）数据中，我们确定了MTNR 1B（编码褪黑激素受体2（MT 2））附近的rs 1387153作为空腹血糖（FPG; P = 1.3 x 10（-7））的调节剂。在欧洲人群中，rs 1387153 T等位基因与FPG升高相关（β = 0.06 mmol/l，P = 7.6 x 10（-29），N = 16，094），2型糖尿病（T2 D）风险（比值比（OR）= 1.15，95% CI = 1.08-1.22，P = 6.3 x 10（-5），病例数= 6，332）和9年内发生高血糖或糖尿病的风险（风险比（HR）= 1.20，95% CI = 1.06-1.36，P = 0.005，事件病例N = 515）。RT-PCR分析证实了MT 2转录本在神经组织中的存在，并显示MT 2在人胰岛和β细胞中表达。我们的数据表明，昼夜节律调节和葡萄糖稳态之间可能存在联系，通过褪黑激素信号通路。
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.