Rose C S, Grarup N, Krarup N T, Poulsen P, Wegner L, Nielsen T, Banasik K, Faerch K, Andersen G, Albrechtsen A, Borch-Johnsen K, Clausen J O, Jørgensen T, Vaag A, Pedersen O, Hansen T
Hagedorn Research Institute, Gentofte, Denmark.
Diabetologia. 2009 Oct;52(10):2122-9. doi: 10.1007/s00125-009-1463-z. Epub 2009 Aug 8.
AIMS/HYPOTHESIS: An association between elevated fasting plasma glucose and the common rs560887 G allele in the G6PC2/ABCB11 locus has been reported. In Danes we aimed to examine rs560887 in relation to plasma glucose and serum insulin responses following oral and i.v. glucose loads and in relation to hepatic glucose production during a hyperinsulinaemic-euglycaemic clamp. Furthermore, we examined rs560887 for association with impaired fasting glycaemia (IFG), impaired glucose tolerance (IGT), type 2 diabetes and components of the metabolic syndrome.
rs560887 was genotyped in the Inter99 cohort (n = 5,899), in 366 young, healthy Danes, in non-diabetic relatives of type 2 diabetic patients (n = 196), and in young and elderly twins (n = 159). Participants underwent an OGTT, an IVGTT or a 2 h hyperinsulinaemic-euglycaemic clamp.
The rs560887 G allele associated with elevated fasting plasma glucose (p = 2 x 10(-14)) but not with plasma glucose levels at 30 min (p = 0.9) or 120 min (p = 0.9) during an OGTT. G allele carriers had elevated levels of serum insulin at 30 min during an OGTT (p = 1 x 10(-4)) and relatives of type 2 diabetes patients carrying the G allele had an increased acute insulin response (p = 4 x 10(-4)) during an IVGTT. Among elderly twins, G allele carriers had higher basal hepatic glucose production (p = 0.04). Finally, the G allele associated with the risk of having IFG (OR 1.26, 95% CI 1.08-1.47, p = 0.002), but not with IGT (OR 0.94, 95% CI 0.82-1.08, p = 0.4) or type 2 diabetes (OR 0.93, 95% CI 0.84-1.04, p = 0.2).
CONCLUSIONS/INTERPRETATION: The common rs560887 G allele in the G6PC2/ABCB11 locus is associated with increased fasting glycaemia and increased risk of IFG, associations that may be partly related to an increased basal hepatic glucose production rate.
目的/假设：已有报道称空腹血糖升高与G6PC2/ABCB11基因座常见的rs560887 G等位基因之间存在关联。在丹麦人群中，我们旨在研究rs560887与口服及静脉注射葡萄糖负荷后血浆葡萄糖和血清胰岛素反应的关系，以及与高胰岛素-正常血糖钳夹期间肝脏葡萄糖生成的关系。此外，我们还研究了rs560887与空腹血糖受损（IFG）、糖耐量受损（IGT）、2型糖尿病及代谢综合征各组分之间的关联。
在Inter99队列（n = 5899）、366名年轻健康的丹麦人、2型糖尿病患者的非糖尿病亲属（n = 196）以及年轻和老年双胞胎（n = 159）中对rs560887进行基因分型。参与者接受了口服葡萄糖耐量试验（OGTT）、静脉注射葡萄糖耐量试验（IVGTT）或2小时高胰岛素-正常血糖钳夹试验。
rs560887 G等位基因与空腹血糖升高相关（p = 2×10⁻¹⁴），但与OGTT期间30分钟（p = 0.9）或120分钟（p = 0.9）的血浆葡萄糖水平无关。G等位基因携带者在OGTT期间30分钟时血清胰岛素水平升高（p = 1×10⁻⁴），携带G等位基因的2型糖尿病患者亲属在IVGTT期间急性胰岛素反应增加（p = 4×10⁻⁴）。在老年双胞胎中，G等位基因携带者的基础肝脏葡萄糖生成较高（p = 0.04）。最后，G等位基因与IFG风险相关（比值比1.26，95%置信区间1.08 - 1.47，p = 0.002），但与IGT（比值比0.94，95%置信区间0.82 - 1.08，p = 0.4）或2型糖尿病（比值比0.93，95%置信区间0.84 - 1.04，p = 0.2）无关。
结论/解读：G6PC2/ABCB11基因座常见的rs560887 G等位基因与空腹血糖升高及IFG风险增加相关，这些关联可能部分与基础肝脏葡萄糖生成率增加有关。
