&ITFKBP5&IT polymorphism is associated with insulin resistance in children and adolescents with obesity
&ITFKBP5&IT polymorphism is associated with insulin resistance in children and adolescents with obesity
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DOI：
10.1016/j.orcp.2016.11.007
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发表时间：
2018-01-01
影响因子：
4.3
通讯作者：
Fichna, Piotr
中科院分区：
文献类型：
--
作者：
Fichna, Marta;Krzysko-Pieczka, Izabela;Fichna, Piotr
目的：由于代谢综合征与皮质醇增多症有一些共同的临床特征，因此推测改变个体糖皮质激素（GC）敏感性的基因可能与肥胖的发病机制及其不良后果有关。 FKBP5 基因编码 GC 受体 (GR) 复合物中的伴侣蛋白，调节类固醇对靶基因的作用。其功能变体 rs1360780 可能增强 FKBP5 基因转录，影响 GR 信号传导，从而影响下丘脑-垂体-肾上腺轴。我们调查了 250 名肥胖儿童和青少年（平均年龄 12.3 +/- 3.6 岁，BMI >= 95%）中 rs1360780 与肥胖和代谢特征的关联。 方法：分析人体测量、身体成分、生化和激素结果。将 rs1360780 的基因分型与 568 名瘦对照进行比较。 结果：8.8% 的肥胖个体存在空腹血糖受损，10.4% 存在葡萄糖耐受不良，2.8% 存在糖尿病，28.8% 肥胖个体存在血脂异常。 143 名患者中有 34 名被诊断为高血压。肥胖受试者和对照组之间的 FKBP5 多态性分布没有发现差异 (p > 0.05)。 rs1360780 分层显示体重和成分没有差异。然而，次要等位基因的携带者表现出胰岛素抵抗增强（p = 0.009）和血清甘油三酯升高（p = 0.006），而所有基因型的胆固醇、HbA1c 和口服葡萄糖激发结果相似。早晨 ACTH 和皮质醇没有差异，但夜间皮质醇在次要等位基因携带者中较高 (p=0.039)，尽管这种关联在逻辑回归分析中丢失。& para;& para;结论：这项研究不支持 FKBP5 与肥胖的关联，但证明了其变异对肥胖相关胰岛素抵抗和高甘油三酯血症易感性的合理暗示。 (C) 2016 年由爱思唯尔有限公司代表亚洲大洋洲肥胖研究协会出版。
Objective: Since metabolic syndrome shares several clinical features with hypercortisolism, it was hypothesised that genes altering individual glucocorticoid (GC) sensitivity might be implicated in pathogenesis of obesity and its adverse outcomes. FKBP5 gene encodes a chaperon protein in the GC receptor (GR) complex, which modulates steroid action upon target genes. Its functional variant, rs1360780, may enhance FKBP5 gene transcription, affect GR signalling and thereby influence the hypothalamo-pituitary-adrenal axis. We investigated the association of rs1360780 with obesity and metabolic characteristics in 250 obese children and adolescents (mean age 12.3 +/- 3.6 years, BMI >= 95th percentile).& para;& para;Methods: Anthropometric measurements, body composition, biochemical and hormonal results were analysed. Genotyping of rs1360780 was compared with 568 lean controls.& para;& para;Results: Impaired fasting glucose was present in 8.8%, glucose intolerance in 10.4%, diabetes in 2.8% and dyslipidemia in 28.8% obese individuals. Hypertension was diagnosed in 34 out of 143 patients. No difference was found in FKBP5 polymorphism distribution between subjects with obesity and controls (p > 0.05). Stratification by rs1360780 revealed no differences in body mass and composition. However, carriers of the minor allele displayed enhanced insulin resistance (p = 0.009) and elevated serum triglyceride (p = 0.006), whereas cholesterol, HbA1c, and oral glucose challenge results were similar for all genotypes. Morning ACTH and cortisol did not differ but evening cortisol was higher in minor allele carriers (p=0.039), although this association was lost in logistic regression analysis.& para;& para;Conclusion: This study does not support the association of FKBP5 with obesity but demonstrates plausible implication of its variant in susceptibility to obesity-related insulin resistance and hypertriglyceridemia. (C) 2016 Published by Elsevier Ltd on behalf of Asia Oceania Association for the Study of Obesity.