Introduction: Corticosteroids are widely prescribed and their use has been linked to adverse cardiometabolic outcomes. A pivotal role in the action of corticosteroids is reserved for the glucocorticoid receptor (GR). Here, we assessed the relationship of glucocorticoid (GC) sensitivity altering GR polymorphisms with anthropometrics and metabolic syndrome (MetS) in corticosteroid users. Methods: In this population-based cohort study (Lifelines) we genotyped 10,621 adult participants for GR hypersensitive (1/2 copies BclI and/or N363S) and GR resistant (1/2 copies ER22/23EK and/or 9β) variants. We assessed the relationship between functional GR polymorphisms with body mass index (BMI), waist circumference (WC), and MetS in users of corticosteroids. Results: Overall corticosteroid use was associated with a significantly higher BMI and WC in GR wild-type users (BMI: +0.63 kg/m2 [0.09-1.16], P=.022; WC: +2.03 cm [0.61-3.44], P=.005) and GR hypersensitive (BMI: mean difference +0.66 kg/m2 [95% CI, 0.31-1.01); WC: +2.06 cm (1.13-2.98), both P<.001), but not in GR resistant users. Significantly higher WC in GR resistant carriers was observed only for inhaled corticosteroid users. With respect to MetS, again only GR wild-type users (OR 1.44 [1.07-1.94], P=.017) and GR hypersensitives (odds ratio (OR) 1.23 [95% CI, 1.00-1.50], P=.046) were more likely to have MetS; even more pronounced in only inhaled corticosteroid users (GR wild-type users, OR 1.64 [1.06-2.55], P=.027; GR hypersensitive users, OR 1.43 [1.08-1.91], P=.013). Conclusions: Polymorphisms associated with increased GR sensitivity and wild-type GR are related to increased BMI, WC and an increased MetS presence in corticosteroid users, especially of the inhaled types, when compared to nonusers. The adverse effects of corticosteroid use are less pronounced in users harboring GR resistant polymorphisms.


中文翻译：

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与糖皮质激素受体多态性相关的人体测量学和代谢综合征

简介： 皮质类固醇被广泛使用，其使用与不良心脏代谢结果有关。糖皮质激素受体 (GR) 在皮质类固醇的作用中起关键作用。在这里，我们评估了糖皮质激素 (GC) 敏感性改变 GR 多态性与皮质类固醇使用者的人体测量学和代谢综合征 (MetS) 的关系。方法：在这项基于人群的队列研究（Lifelines）中，我们对 10,621 名成人参与者进行了 GR 过敏（1/2 拷贝 BclI 和/或 N363S）和 GR 抗性（1/2 拷贝 ER22/23EK 和/或 9β）变体的基因分型。我们评估了皮质类固醇使用者的功能性 GR 多态性与体重指数 (BMI)、腰围 (WC) 和代谢综合征之间的关系。结果：总体皮质类固醇的使用与 GR 野生型使用者的 BMI 和 WC 显着升高相关（BMI：+0.63 kg/m2 [0.09-1.16]，P=.022；WC：+2.03 cm [0.61-3.44]，P= .005）和 GR 过敏（BMI：平均差 +0.66 kg/m2 [95% CI，0.31-1.01）；WC：+2.06 cm (1.13-2.98)，均 P<.001)，但在 GR 抗性用户中没有。仅在吸入皮质类固醇使用者中观察到 GR 耐药携带者的 WC 显着升高。关于 MetS，同样只有 GR 野生型用户（OR 1.44 [1.07-1.94]，P=.017）和 GR 过敏者（优势比 (OR) 1.23 [95% CI，1.00-1.50]，P=.046 ) 更有可能患有 MetS；仅在吸入皮质类固醇使用者中更为明显（GR 野生型使用者，OR 1.64 [1.06-2.55]，P=.027；GR 过敏使用者，OR 1.43 [1.08-1.91]，P=.013）。结论：与非使用者相比，与 GR 敏感性增加和野生型 GR 相关的多态性与皮质类固醇使用者（尤其是吸入型）的 BMI、WC 和 MetS 增加有关。在携带 GR 抗性多态性的使用者中，使用皮质类固醇的不利影响不太明显。