基因多态和抗发作药物诱导的不良反应在秘鲁患者中CYP2C9和CYP2C19之间的关联
Angel T Alvarado1, Felipe L Ignacio-Cconchoy2,3, Juan C Espinoza-Retuerto4,5
1Center for Research in Molecular Pharmacology and 4P Medicine, VRI, San Ignacio de Loyola University, La Molina, Lima 15024, Peru.
在CYP2C9和CYP2C19中的遗传变异增加了秘鲁患者药物不良反应的风险. 基因定型这些基因和避免多疗法可以提高抗发作药物的安全性.
科学领域:
- 药物基因组学 药物基因组学
- 临床药理学 临床药理学
- 的研究研究.
背景情况:
- 影响全球超过5000万,在秘鲁有显著的患病率.
- 抗发作药物 (ASM) 对管理至关重要,但可能导致药物不良反应 (ADR).
- 遗传因素,特别是CYP2C9和CYP2C19等药物代谢酶中的多态性,可能会影响ASM的疗效和安全性.
研究的目的:
- 在秘鲁患者中调查CYP2C9和CYP2C19遗传多态性和ASM诱导的ADR之间的关联.
- 评估与这些基因相关的代谢表型对ADR风险的影响.
- 确定多疗法作为该人群中潜在的副作用风险因素.
主要方法:
- 一项涉及89名秘鲁患者的描述性观察性研究.
- 从血液样本中提取基因组DNA.
- 使用实时PCR和TaqMan探测器对CYP2C9 (*2, *3) 和CYP2C19 (*2, *3, *17) 等位基因的基因定型.
主要成果:
- 对于CYP2C9和CYP2C19的中间/差代谢器表型的患者,副作用的风险明显更高 (OR = 3.75).
- 功能减弱的等位基因CYP2C9*2,CYP2C9*3和CYP2C19*2与ADR风险增加有关.
- 多疗法被确定为副作用的显著预测因素 (OR = 4.33).
结论:
- 在秘鲁的患者中,CYP2C9和CYP2C19遗传变异与ASM引起的ADR风险增加有关.
- 由于特定的等位基因而降低的代谢活性会增加ADR风险.
- 基因定型CYP2C9和CYP2C19,以及仔细考虑多疗法,对于优化拉丁美洲ASM安全性具有临床意义.
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