The Impact of Genetic Variation in the G6PC2 Gene on Insulin Secretion Depends on Glycemia
The Impact of Genetic Variation in the G6PC2 Gene on Insulin Secretion Depends on Glycemia
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DOI：
10.1210/jc.2010-0860
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发表时间：
2010-12-01
影响因子：
5.8
通讯作者：
Fritsche, Andreas
中科院分区：
文献类型：
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作者：
Heni, Martin;Ketterer, Caroline;Fritsche, Andreas
背景：G6 PC 2基因座内的单核苷酸多态性（SNP）与空腹血糖和胰岛素分泌相关。这些SNPs与2型糖尿病风险无关。目的：我们的目的是调查SNP对葡萄糖刺激的胰岛素分泌变量的影响是否受葡萄糖耐量状态的影响。设计、设置、参与者和干预：在这项横断面研究中，我们对1505名健康高加索受试者进行基因分型[正常葡萄糖耐量（NGT），1098;葡萄糖耐量受损（IGT）/空腹血糖受损（IFG），407]。一个由326名受试者组成的亚组进行了静脉葡萄糖耐量试验，512名参与者参加了高胰岛素-正常血糖钳夹试验。为了复制，SNP rs 560887基因分型457例受试者（NGT，265; IGT，192）从四个独立的德国和荷兰的研究谁经历了高血糖clamp.Main结果Measure：胰岛素分泌evaluated.Results：主要G-等位基因携带者表现出增加空腹血糖（P < 0.0001）。胰岛素敏感性和分泌与SNP无关（P >= 0.06）。糖耐量状态和基因型对胰岛素分泌有交互作用（P = 0.036），在NGT受试者中，rs 560887的次要A等位基因与胰岛素生成指数降低相关（P = 0.044），而IFG/IGT受试者中的情况并非如此（P = 1.0）。在静脉葡萄糖耐量试验中，仅在NGT受试者中观察到A等位基因携带者与第一时相胰岛素分泌减少的相关性（P = 0.0053）。同样，在高血糖钳夹组中，A-等位基因与第一时相胰岛素分泌减少仅在NGT组（P = 0.022），但不是在IGT group.Conclusions：高血糖对胰岛素分泌的影响盖过了更微妙的影响，在G6 PC 2基因座对胰岛素分泌。（临床内分泌代谢杂志95：E479-E484，2010）
Context: Single-nucleotide polymorphisms (SNPs) within the G6PC2 locus are associated with fasting glucose and insulin secretion. These SNPs are not associated with type 2 diabetes risk.Objective: Our objective was to investigate whether the impact of the SNP on variables of glucose-stimulated insulin secretion is influenced by glucose tolerance status.Design, Setting, Participants, and Intervention: In this cross-sectional study, we genotyped 1505 healthy Caucasian subjects [normal glucose tolerance (NGT), 1098; impaired glucose tolerance (IGT)/impaired fasting glucose(IFG), 407] for SNP rs560887 within the G6PC2 locus. A subgroup of 326 subjects underwent an iv glucose tolerance test, and 512 participants took part in a hyperinsulinemic-euglycemic clamp. For replication, SNP rs560887 was genotyped in 457 subjects(NGT, 265; IGT, 192) from four independent German and Dutch studies who underwent a hyperglycemic clamp.Main Outcome Measure: Insulin secretion was evaluated.Results: Carriers of the major G-allele exhibited increased fasting glycemia (P < 0.0001). Insulin sensitivity and secretion were not associated with the SNP (P >= 0.06). Glucose tolerance status and genotype interacted on insulin secretion (P = 0.036), such that in NGT subjects, the minor A-allele of rs560887 was associated with decreased insulinogenic index (P = 0.044), which was not the case in subjects with IFG/IGT (P = 1.0). During the iv glucose tolerance test, an association of A-allele carriers with decreased first-phase insulin secretion was also observed only in NGT subjects (P = 0.0053). Likewise, in the hyperglycemic clamp group, the A-allele was associated with decreased first-phase insulin secretion only in the NGT group (P = 0.022) but not in the IGT group.Conclusions: The effects of hyperglycemia on insulin secretion override the more subtle effects of genetic variation in the G6PC2 locus on insulin secretion. (J Clin Endocrinol Metab95: E479-E484, 2010)