儿童短期使用葡萄糖皮质体的隐患:基因组分析
Xiaolin Xu1, Yan Li2, Tongxin Han2
1Department of Immunity, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China; Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China.
遗传因素影响葡萄糖皮质类药物不良反应 (ADRs). 这项研究确定了ABCB1和CYP3A5的高风险变体,表明需要在儿童中进行个性化GC治疗.
科学领域:
- 药物基因组学 药物基因组学
- 儿科药理学 儿科药理学
- 药物新陈代谢 药物新陈代谢
背景情况:
- 葡萄糖皮质类药物 (GCs) 即使短期使用也可能引起药物不良反应 (ADRs).
- 在GC诱导的ADR中,个体间的变异性表明遗传因素的作用.
- 介绍了一个儿童在短时间服用GC后体重增加和骨质疏松症的病例.
研究的目的:
- 为了研究GC诱导的ADRs的遗传基础.
- 在儿科队列中分析特定基因变异与GC毒性的关联.
主要方法:
- 整体外基因组测序 (WES) 用于基因组分析.
- 在大型儿科队列 (分别为52,119和37,884名儿童) 中对ABCB1rs1045642和CYP3A5rs776746进行基因型鉴定.
- 药物代谢,运输和向途径的分析.
主要成果:
- 在ABCB1 rs1045642中的高风险变体和CYP3A5 rs776746中的缓慢代谢变体被确定为GC-ADRs的潜在贡献者.
- ABCB1 rs1045642 CT和TT类型的患病率分别为47.58%和15.69%.
- 在CYP3A5 rs776746基因型中,出现了CC (50.54%),CT (41.15%) 和TT (8.31%).
- 中国儿科人口中,ABCB1的中间代谢类型<50%,CYP3A5.5的慢代谢类型高达90%.
结论:
- 在ABCB1和CYP3A5的等位基因突变显著影响GC的有效性和安全性.
- 基因评估对于个性化GC疗法至关重要,特别是在中国儿科患者中.
- 研究结果强调需要考虑药物遗传学来优化GC治疗和预防ADR.
更多相关视频
13:22A Chemical Screening Procedure for Glucocorticoid Signaling with a Zebrafish Larva Luciferase Reporter System
Published on: September 10, 2013
11:31Rapid Fractionation and Isolation of Whole Blood Components in Samples Obtained from a Community-based Setting
Published on: November 30, 2015
相关概念视频
Adrenal Gland Disorders
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...
Hypoglycemia and Glucagon
Hormones of the Adrenal Glands
The adrenal cortex, a powerhouse of hormone synthesis, generates over two dozen corticosteroid hormones. The zona glomerulosa produces mineralocorticoids, exemplified by aldosterone, influencing the electrolyte composition of body fluids. The synthesis of glucocorticoids such as cortisol and...
Antiasthma Drugs: Inhaled Corticosteroids and Glucocorticoids
ICS work through a multifaceted mechanism of action. They suppress the inflammatory response caused by the proliferation of TH cells. They also reduce the transcription of the IL-2 gene, which is involved in the...
Nature and Nurture
Insulin: Dosing Regimen and Adverse Effects
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
