Sheu W H, Lee W J, Lin L Y, Chang R L, Chen Y T
Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
Metabolism. 2001 Dec;50(12):1447-51. doi: 10.1053/meta.2001.27192.
It is well established that, as a group, patients with essential hypertension are characterized by insulin resistance. Previous studies have shown that a biallelic polymorphism in the tumor necrosis factor (TNF)alpha promoter position -308 and -238 might be involved in the insulin resistance state in diabetic and/or nondiabetic subjects. We determined these polymorphisms in 235 nondiabetic hypertensive subjects and 246 unrelated normotensive controls. Fasting plasma glucose, insulin, lipoprotein, leptin, and TNFalpha concentrations were measured, in addition to plasma glucose and insulin responses to a 75-g oral glucose tolerance test (OGTT). Insulin sensitivity was also determined by an insulin suppression test in 69 hypertensive and 76 normotensive individuals. The results showed no association of these genotypic distributions between hypertensive and normotensive individuals both at -308 (GG, GA, and AA were 80.9%, 17.9%, and 1.3% in hypertensives, 84.2%, 15.4%, and 0.4% in normotensives, chi(2) = 1.68, P =.432) and at -238 (GG, GA, and AA were 98.3%, 1.7%, and 0% in hypertensives, 96.7%, 3.3%, and 0% in normotensives, chi(2) = 1.19, P =.276) sites. These results did not change even after adjustment for values of age and body mass index (BMI). Anthropometric measurements, fasting plasma glucose, insulin, lipoprotein concentrations, glucose, and insulin responses to OGTT, TNFalpha, and leptin concentrations were similar between the genotype at the -308 site both in hypertensive and normotensive groups. Insulin sensitivity, either measured by an insulin suppression test or homeostasis model assessment (HOMA) index, did not differ between the genotype at the -308 site in subjects with hypertension or normotension. Fasting plasma TNFalpha (10.2 alpha 0.5 pg/mL v 10.1 +/- 0.5 pg/mL, P =.928) concentrations did not differ between hypertensive and normotensive subjects even after adjustment for body fat and BMI values. We conclude that TNFalpha promoter gene polymorphisms at position -238 and -308 do not play a major role in the pathogenesis of insulin resistance in Chinese subjects with or without hypertension.
众所周知，原发性高血压患者群体具有胰岛素抵抗的特征。先前的研究表明，肿瘤坏死因子（TNF）α启动子位置-308和-238处的双等位基因多态性可能与糖尿病和/或非糖尿病受试者的胰岛素抵抗状态有关。我们在235名非糖尿病高血压受试者和246名无亲缘关系的正常血压对照者中确定了这些多态性。除了测量空腹血糖、胰岛素、脂蛋白、瘦素和TNFα浓度外，还测量了口服75克葡萄糖耐量试验（OGTT）后的血糖和胰岛素反应。还通过胰岛素抑制试验在69名高血压患者和76名正常血压个体中测定了胰岛素敏感性。结果显示，在-308位点（高血压患者中GG、GA和AA分别为80.9%、17.9%和1.3%，正常血压者中分别为84.2%、15.4%和0.4%，χ² = 1.68，P = 0.432）和-238位点（高血压患者中GG、GA和AA分别为98.3%、1.7%和0%，正常血压者中分别为96.7%、3.3%和0%，χ² = 1.19，P = 0.276），高血压患者和正常血压个体之间这些基因型分布均无关联。即使在对年龄和体重指数（BMI）值进行校正后，这些结果也没有改变。在-308位点的基因型方面，高血压组和正常血压组的人体测量指标、空腹血糖、胰岛素、脂蛋白浓度、葡萄糖和胰岛素对OGTT的反应、TNFα和瘦素浓度相似。通过胰岛素抑制试验或稳态模型评估（HOMA）指数测量的胰岛素敏感性，在高血压或正常血压受试者中-308位点的基因型之间没有差异。即使在对体脂和BMI值进行校正后，高血压患者和正常血压受试者的空腹血浆TNFα浓度（10.2±0.5 pg/mL对10.1±0.5 pg/mL，P = 0.928）也没有差异。我们得出结论，-238和-308位点的TNFα启动子基因多态性在有或无高血压的中国受试者胰岛素抵抗的发病机制中不发挥主要作用。
