在混合人群中进行药物遗传测试:分子病理学协会药物遗传学工作组的频率1级 巴西人的变异性基因
1Clinical Research and Technological Development Division, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.
The Journal of molecular diagnostics : JMD
|January 25, 2025
概括
巴西的药物遗传变异频率有很大的不同,有些缺席,有些则是常见的. 对于药物遗传学测试小组的建议应该考虑人口多样性,而不是种族.
科学领域:
- 药物基因组学 药物基因组学
- 遗传学 遗传学 是一个
- 人口健康 人口健康
背景情况:
- 药物遗传学 (PGx) 测试对于个性化医学至关重要.
- 分子病理学协会 (AMP) 为1级PGx变种提供了建议.
- 了解巴西等多元人口中的变异频率对于有效实施至关重要.
研究的目的:
- 确定1级药物遗传变异在混合的巴西人群中的频率分布.
- 评估AMP建议适用于巴西药物遗传学测试小组的适用性.
- 为巴西人设计药物遗传检测策略提供信息,考虑到人口多样性.
主要方法:
- 对两个大型群体 (>1000个人) 的巴西人口混合的分析.
- 包括来自巴西公共卫生系统的患者在药物遗传学试验中.
- 基于AMP建议的1级药物遗传变异的频率分布的检查.
主要成果:
- 在DPYD中缺少三种1级变异,这表明可能被排除在巴西基因型化小组之外.
- 13个变体的频率≤1.0%,而21个变体的频率从1.2% (NUDT15*3) 到76.4% (CYP3A5*3).
- 由于祖先变异,在巴西种族/肤色类别中观察到变异频率 (CYP2C9,CYP2D6,CYP3A4,VKORC1) 的显著差异.
- 美国原住民群体表现出不同的变体频率 (NUDT15*3,TPMT*3A,CYP2C19*17).
结论:
- 巴西的药物遗传变异频率多样化,受到祖先的影响.
- 种族/肤色类别不足以指导巴西的药物遗传学测试小组选择或剂量指南.
- 在巴西设计和实施药物遗传学测试小组时,必须考虑人口多样性,包括像美洲原住民这样的代表性不足的群体.
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