Common genetic variation in the melatonin receptor 1B gene (MTNR1B) is associated with decreased early-phase insulin response.
Common genetic variation in the melatonin receptor 1B gene (MTNR1B) is associated with decreased early-phase insulin response.
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DOI：
10.1007/s00125-009-1392-x
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发表时间：
2009-08
期刊：
影响因子：
8.2
通讯作者：
RISC Consortium
中科院分区：
文献类型：
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作者：
Langenberg C;Pascoe L;Mari A;Tura A;Laakso M;Frayling TM;Barroso I;Loos RJ;Wareham NJ;Walker M;RISC Consortium
我们研究了 MTNR1B 的变异是否与 β 细胞功能和全身胰岛素敏感性的测量相关，MTNR1B 最近被确定为健康、无糖尿病个体空腹血糖水平的常见遗传决定因素。我们对 19 个胰岛素敏感性与心血管疾病之间的关系 (RISC) 研究中心的 1,276 名欧洲血统健康个体进行了研究。通过正常血糖-高胰岛素钳夹评估全身胰岛素敏感性，β细胞功能指数源自75克口服葡萄糖耐量试验（包括30分钟胰岛素反应和葡萄糖敏感性）。我们使用加性遗传模型研究了 MTNR1B 中的 rs10830963，调整了年龄、性别和招募中心。 MTNR1B 中 rs10830963 的次要 (G) 等位基因（HapMap Center d’Etude du Polymorphisme [具有北欧和西欧血统的犹他州居民] [CEU] 中的频率为 0.30；RISC 参与者中为 0.29）与较高水平的空腹血糖相关（标准化 β [95% CI] 0.17 [0.085, 0.25]/ G等位基因，p = 5.8 × 10−5)，与最近的观察结果一致。此外，G等位基因与较低的早期胰岛素反应显着相关（-0.19 [-0.28，-0.10]，p = 1.7 × 10−5），以及β细胞葡萄糖敏感性降低（-0.11 [-0.20，-0.027]，p = 0.010）。没有观察到与钳夹评估的胰岛素敏感性（p = 0.15）或不同的身体尺寸测量（所有p > 0.7）之间的关联。 MTNR1B 的遗传变异与早期胰岛素反应缺陷和 β 细胞葡萄糖敏感性降低有关，这可能导致 MTNR1B 中携带 rs10830963 次要 G 等位基因的非糖尿病个体血糖水平较高。本文的在线版本 (doi:10.1007/s00125-009-1392-x) 包含 RISC 联盟的成员列表，可供授权用户使用。
We investigated whether variation in MTNR1B, which was recently identified as a common genetic determinant of fasting glucose levels in healthy, diabetes-free individuals, is associated with measures of beta cell function and whole-body insulin sensitivity. We studied 1,276 healthy individuals of European ancestry at 19 centres of the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study. Whole-body insulin sensitivity was assessed by euglycaemic–hyperinsulinaemic clamp and indices of beta cell function were derived from a 75 g oral glucose tolerance test (including 30 min insulin response and glucose sensitivity). We studied rs10830963 in MTNR1B using additive genetic models, adjusting for age, sex and recruitment centre. The minor (G) allele of rs10830963 in MTNR1B (frequency 0.30 in HapMap Centre d’Etude du Polymorphisme [Utah residents with northern and western European ancestry] [CEU]; 0.29 in RISC participants) was associated with higher levels of fasting plasma glucose (standardised beta [95% CI] 0.17 [0.085, 0.25] per G allele, p = 5.8 × 10−5), consistent with recent observations. In addition, the G-allele was significantly associated with lower early insulin response (−0.19 [−0.28, −0.10], p = 1.7 × 10−5), as well as with decreased beta cell glucose sensitivity (−0.11 [−0.20, −0.027], p = 0.010). No associations were observed with clamp-assessed insulin sensitivity (p = 0.15) or different measures of body size (p > 0.7 for all). Genetic variation in MTNR1B is associated with defective early insulin response and decreased beta cell glucose sensitivity, which may contribute to the higher glucose levels of non-diabetic individuals carrying the minor G allele of rs10830963 in MTNR1B. The online version of this article (doi:10.1007/s00125-009-1392-x) contains a list of the members of the RISC Consortium, which is available to authorised users.