Department of Human Biology, Maastricht University, Maastricht, The Netherlands.
Clin Endocrinol (Oxf). 2011 Jun;74(6):679-86. doi: 10.1111/j.1365-2265.2011.03985.x.
The relationship between hypothalamus/pituitary/adrenal (HPA) axis functioning and (visceral) obesity may be explained by single-nucleotide polymorphisms (SNPs) of the HPA axis. Objective To investigate the relationship between the HPA axis SNP's 'BclI' in the glucocorticoid receptor gene and C8246T in the POMC gene and anthropometric measurements, body composition, 5-h cortisol concentrations, HPA axis feedback sensitivity, as well as HPA axis feedback sensitivity under stress in men and women. DESIGN/SUBJECTS/MEASUREMENTS: We assessed in 92 men and 102 women (18-55 years, BMI 19-41 kg/m(2) ) anthropometry, body composition using hydrodensitometry and deuterium dilution method, cortisol variability by measuring 5-h cortisol concentrations, HPA axis feedback functioning using a dexamethasone suppression test and HPA axis functioning under a challenged condition consisting of a standardized high intensity test with ingestion of 4 mg dexamethasone.
In female participants, the 8246C allele carriers compared to the 8246T allele carries were associated with a higher 5-h cortisol exposure (1·52 × 10(5) ± 0·8 vs 1·18 × 10(5) ± 0·6 nm·min, P < 0·05) and higher baseline postdexamethasone cortisol concentrations (54·5 ± 35·6 vs 37·4 ± 18·5 nm, P < 0·05). In male participants regarding the C8246T allele carriers and in both male and female participants regarding the BclI genotypes, no significant differences in anthropometric measurements, body composition and HPA axis functioning were observed. Multiple regression analysis showed that only increased 5-h cortisol exposure significantly related to changes in anthropometric measurements and body composition; the BclI and C8246T genotypes were not associated.
Our preliminary data show that in both men and women (18-55 years, BMI 19-41 kg/m(2) ), the SNP's BclI and C8246T of the HPA axis were primarily related to altered HPA axis functioning, rather than to altered anthropometric measurements and body composition.
下丘脑-垂体-肾上腺（HPA）轴功能与（内脏）肥胖之间的关系可能可以用 HPA 轴的单核苷酸多态性（SNP）来解释。目的：研究糖皮质激素受体基因中的 HPA 轴 SNP“BclI”和 POMC 基因中的 C8246T 与人体测量学、身体成分、5 小时皮质醇浓度、HPA 轴反馈敏感性以及男女应激下 HPA 轴反馈敏感性之间的关系。设计/受试者/测量方法：我们评估了 92 名男性和 102 名女性（18-55 岁，BMI 19-41kg/m2）的人体测量学、使用比重计和氘稀释法测量的身体成分、5 小时皮质醇浓度的可变性、使用地塞米松抑制试验测量的 HPA 轴反馈功能以及由摄入 4mg 地塞米松的标准化高强度试验组成的应激下 HPA 轴功能。结果：在女性参与者中，与 8246T 等位基因携带者相比，8246C 等位基因携带者的 5 小时皮质醇暴露量更高（1.52×105±0.8vs1.18×105±0.6nm·min，P<0.05），基础后地塞米松皮质醇浓度更高（54.5±35.6vs37.4±18.5nm，P<0.05）。在男性参与者中，关于 C8246T 等位基因携带者，以及在男性和女性参与者中，关于 BclI 基因型，人体测量学、身体成分和 HPA 轴功能均未见显著差异。多元回归分析表明，只有增加的 5 小时皮质醇暴露量与人体测量学和身体成分的变化显著相关；BclI 和 C8246T 基因型与变化无关。结论：我们的初步数据表明，在 18-55 岁、BMI 19-41kg/m2 的男性和女性中，HPA 轴的 SNP BclI 和 C8246T 主要与 HPA 轴功能改变有关，而不是与人体测量学和身体成分改变有关。
