The tumour necrosis factor alpha –238 G → A and –308 G → A promoter polymorphisms are not associated with insulin sensitivity and insulin secretion in young healthy relatives of Type II Diabetic patients
The tumour necrosis factor alpha –238 G → A and –308 G → A promoter polymorphisms are not associated with insulin sensitivity and insulin secretion in young healthy relatives of Type II Diabetic patients
复制标题
肿瘤坏死因子α –238 G → A 和 –308 G → A 启动子多态性与 II 型糖尿病患者年轻健康亲属的胰岛素敏感性和胰岛素分泌无关
作者：
M. Koch;K. Rett;A. Volk;E. Maerker;K. Haist;M. Weisser;A. Rettig;W. Renn;HU Häring
目的/假设。肿瘤坏死因子-α（TNF-α）被认为影响骨骼肌胰岛素抵抗。TNF-α启动子区-238和-308位点的两个G → A转换可能参与该基因的转录调控。胰岛素抵抗是一种独立的家族性特征，可预测II型（非胰岛素依赖型）糖尿病的发生。我们在一组II型糖尿病患者的年轻健康亲属中研究了两种多态性对胰岛素敏感性和胰岛素分泌的影响。我们检查了109名有II型糖尿病病史的白人患者的一级亲属，他们进行了广泛代谢和人体测量表型分析，并确定了TNF-α-238和-308 G→ A启动子多态性。对于-238多态性，83名先证者（76.1%）为G等位基因纯合子，25名先证者（22.9%）为杂合子，1名先证者（0.9%）为A等位基因纯合子。对于-308多态性，83名先证者（76.1%）为G等位基因纯合，24名先证者（22.0%）为杂合，2名先证者（1.18%）为A等位基因纯合。有和没有多态性的先证者在胰岛素敏感性（p = 0.78）、口服葡萄糖耐量试验中的胰岛素浓度和C肽浓度（p > 0.05）方面没有差异。在我们的队列中，我们无法检测到胰岛素敏感性或胰岛素分泌与TNF-α启动子多态性之间的关联。这些多态性在胰岛素敏感性低或高的先证者中出现的频率相同。[Diabetologia（2000）43：181-184]
Aims/hypothesis. Tumour necrosis factor-α (TNF-α) is believed to influence skeletal muscle insulin resistance. Two G → A transitions in the promoter region of TNF-α at position –238 and –308 have been identified that could play a part in transcriptional regulation of the gene. Insulin resistance is an independent familial trait that predicts the development of Type II (non-insulin-dependent) diabetes mellitus. We investigated the influence on insulin sensitivity and insulin secretion of both polymorphisms in a cohort of young healthy relatives of patients with Type II diabetes.¶Methods. We examined 109 first-degree relatives of Caucasian patients with a history of Type II diabetes, who underwent extensive metabolical and anthropometrical phenotyping, and determined the TNF-α–238 and –308 G→ A promoter polymorphisms.¶Results. For the –238 polymorphism, 83 probands (76.1 %) were homozygous for the G-allele, 25 probands (22.9 %) were heterozygous and 1 proband (0.9 %) was homozygous for the A-allele. For the –308 polymorphism, 83 probands (76.1 %) were homozygous for the G-allele, 24 probands (22.0 %) were heterozygous and 2 probands (1.18 %) were homozygous for the A-allele. Probands with and without the polymorphism did not differ in insulin sensitivity (p = 0.78), insulin-concentrations and C-peptide concentrations in oral glucose tolerance tests (p > 0.05).¶Conclusions/interpretation. We could not detect an association between insulin sensitivity or insulin secretion and TNF-α promoter polymorphisms in our cohort. The polymorphisms occur at the same frequencies in probands with either low or high insulin sensitivity. [Diabetologia (2000) 43: 181–184]
影响因子：
39.2
作者：
WARRAM, JH;MARTIN, BC;KAHN, CR
通讯作者：
KAHN, CR