Nürnberger Jens, Dammer Sandra, Philipp Thomas, Wenzel Rene R, Schäfers Rafael F
Division of Nephrology and Hypertension, University of Essen, Hufelandstrasse 55, 45122 Essen, Germany.
Cardiovasc Diabetol. 2003 Jun 25;2:7. doi: 10.1186/1475-2840-2-7.
A C825T polymorphism was recently identified in the gene encoding the beta3 subunit of heterotrimeric G-proteins (GNB3). The T-allele is significantly associated with essential hypertension and obesity. In order to further explore a possible pathogenetic link between the T-allele and impaired glucose tolerance we studied metabolic and haemodynamic responses to oral glucose loading in young, healthy subjects with and without the 825T-allele.
Twelve subjects with and 10 without the 825T-allele were investigated at rest and following glucose ingestion (75 g). Blood glucose, serum insulin and haemodynamics were determined prior to and over 2 hours following glucose ingestion. We non-invasively measured stroke volume (SV, by impedance-cardiography), blood pressure (BP), heart rate (HR), and systolic-time-intervals. Cardiac output (CO) was calculated from HR and SV. Total peripheral resistance was calculated from CO and BP. Metabolic and haemodynamic changes were quantified by maximal responses and by calculation of areas under the concentration time profile (AUC). Significances of differences between subjects with and without the T-allele were determined by unpaired two-tailed t-tests. A p < 0.05 was considered statistically significant.
Metabolic and haemodynamic parameters at baseline were very similar between both groups. The presence of the T-allele did not alter the response of any metabolic or haemodynamic parameter to glucose loading.
In conclusion, this study does not support the hypothesis that the C825T polymorphism may serve as a genetic marker of early impaired glucose tolerance.
最近在异源三聚体G蛋白（GNB3）β3亚基编码基因中发现了一个C825T多态性。T等位基因与原发性高血压和肥胖显著相关。为了进一步探究T等位基因与糖耐量受损之间可能的发病机制联系，我们研究了有或无825T等位基因的年轻健康受试者口服葡萄糖负荷后的代谢和血流动力学反应。
对12名有825T等位基因和10名无该等位基因的受试者在静息状态及口服葡萄糖（75克）后进行研究。在口服葡萄糖前及之后2小时内测定血糖、血清胰岛素和血流动力学指标。我们通过阻抗心动图非侵入性测量每搏输出量（SV）、血压（BP）、心率（HR）和收缩期时间间期。心输出量（CO）由HR和SV计算得出。总外周阻力由CO和BP计算得出。代谢和血流动力学变化通过最大反应以及浓度时间曲线下面积（AUC）计算进行量化。有或无T等位基因受试者之间差异的显著性通过非配对双尾t检验确定。p < 0.05被认为具有统计学意义。
两组基线时的代谢和血流动力学参数非常相似。T等位基因的存在并未改变任何代谢或血流动力学参数对葡萄糖负荷的反应。
总之，本研究不支持C825T多态性可能作为早期糖耐量受损遗传标志物的假说。
