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A Polymorphism in the Glucocorticoid Receptor Gene, Which Decreases Sensitivity to Glucocorticoids In Vivo, Is Associated With Low Insulin and Cholesterol Levels
Diabetes ( IF 6.2 ) Pub Date : 2002-10-01 , DOI: 10.2337/diabetes.51.10.3128
Elisabeth F C van Rossum 1 , Jan W Koper , Nannette A T M Huizenga , André G Uitterlinden , Joop A M J L Janssen , Albert O Brinkmann , Diederick E Grobbee , Frank H de Jong , Cornelia M van Duyn , Huibert A P Pols , Steven W J Lamberts
Affiliation  

We investigated whether a polymorphism in codons 22 and 23 of the glucocorticoid (GC) receptor gene [GAGAGG(GluArg) --> GAAAAG(GluLys)] is associated with altered GC sensitivity, anthropometric parameters, cardiovascular risk factors, and sex steroid hormones. In a subgroup of 202 healthy elderly subjects of the Rotterdam Study, we identified 18 heterozygotes (8.9%) for the 22/23EK allele (ER22/23EK carriers). In the highest age group, the number of ER22/23EK carriers was higher (67-82 years, 12.9%) than in the youngest age group (53-67 years, 4.9%; P < 0.05). Two dexamethasone (DEX) suppression tests with 1 and 0.25 mg DEX were performed, and serum cortisol and insulin concentrations were compared between ER22/23EK carriers and noncarriers. After administration of 1 mg DEX, the ER22/23EK group had higher serum cortisol concentrations (54.8 +/- 18.3 vs. 26.4 +/- 1.4 nmol/l, P < 0.0001), as well as a smaller decrease in cortisol (467.0 +/- 31.7 vs. 484.5 +/- 10.3 nmol/l, P < 0.0001). ER22/23EK carriers had lower fasting insulin concentrations (P < 0.001), homeostasis model assessment- insulin resistance (IR) (index of IR, P < 0.05), and total (P < 0.02) and LDL cholesterol concentrations (P < 0.01). Our data suggest that carriers of the 22/23EK allele are relatively more resistant to the effects of GCs with respect to the sensitivity of the adrenal feedback mechanism than noncarriers, resulting in a better metabolic health profile.

中文翻译:

降低体内对糖皮质激素敏感性的糖皮质激素受体基因的多态性与低胰岛素和胆固醇水平有关

我们研究了糖皮质激素 (GC) 受体基因 [GAGAGG(GluArg) --> GAAAAG(GluLys)] 密码子 22 和 23 的多态性是否与改变的 GC 敏感性、人体测量参数、心血管危险因素和性类固醇激素有关。在鹿特丹研究的 202 名健康老年受试者的亚组中,我们确定了 22/23EK 等位基因(ER22/23EK 携带者)的 18 个杂合子 (8.9%)。在最高年龄组中,ER22/23EK 携带者的数量(67-82 岁,12.9%)高于最年轻年龄组(53-67 岁,4.9%;P < 0.05)。使用 1 和 0.25 毫克 DEX 进行了两次地塞米松 (DEX) 抑制试验,比较了 ER22/23EK 携带者和非携带者之间的血清皮质醇和胰岛素浓度。给予 1 mg DEX 后,ER22/23EK 组的血清皮质醇浓度更高(54. 8 +/- 18.3 与 26.4 +/- 1.4 nmol/l,P < 0.0001),以及皮质醇的较小下降(467.0 +/- 31.7 与 484.5 +/- 10.3 nmol/l,P < 0.0001) . ER22/23EK 携带者具有较低的空腹胰岛素浓度 (P < 0.001)、稳态模型评估 - 胰岛素抵抗 (IR)(IR 指数,P < 0.05)以及总胆固醇 (P < 0.02) 和 LDL 胆固醇浓度 (P < 0.01) . 我们的数据表明,与非携带者相比,22/23EK 等位基因的携带者对 GC 的影响相对更能抵抗肾上腺反馈机制的敏感性,从而导致更好的代谢健康状况。稳态模型评估 - 胰岛素抵抗 (IR)(IR 指数,P < 0.05),以及总胆固醇(P < 0.02)和 LDL 胆固醇浓度(P < 0.01)。我们的数据表明,与非携带者相比,22/23EK 等位基因的携带者对 GC 的影响相对更能抵抗肾上腺反馈机制的敏感性,从而导致更好的代谢健康状况。稳态模型评估 - 胰岛素抵抗 (IR)(IR 指数,P < 0.05),以及总胆固醇(P < 0.02)和 LDL 胆固醇浓度(P < 0.01)。我们的数据表明,与非携带者相比,22/23EK 等位基因的携带者对 GC 的影响相对更能抵抗肾上腺反馈机制的敏感性,从而导致更好的代谢健康状况。
更新日期:2002-10-01
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