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通过自我报告的祖先估计虚假阴性药物遗传测试结果的频率

Weng-Sam Siu¹, Abdullah Al Maruf^2,3,4,5, Sarker M Shaheen^4,5

¹Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

Clinical pharmacology and therapeutics

|April 27, 2025

概括

药物遗传学 (PGx) 测试显示基因变异频率的祖先差异. 需要扩大PGx面板,以减少假阴性结果,并改善所有人群的测试公平性.

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
临床药理学临床药理学

背景情况:

药物遗传学 (PGx) 研究在历史上代表非欧洲人口不足.
这种差异引发了人们对当前PGx测试面板在不同祖先群体中的适用性的担忧.
代表人数不足会导致非欧洲人的假阴性结果增加.

研究的目的:

为了研究药物基因参考等位基因 (*1) 和基因型 (*1/*1) 频率的基于祖先的差异.
评估不同祖先群体的PGx测试中假阴性结果的可能性.
评估PGx面板中扩大等位基因覆盖范围的需要.

主要方法:

通过自我报告的祖先对1086名年轻人 (6-24岁) 的队列进行了评估 *1和 *1/*1等位基因频率.
使用了PGx面板,涵盖了10种药物基因的所有分子病理学会Tier 1等位基因和53%的Tier 2等位基因.
欧洲 (n=727) 和非欧洲 (n=359) 参与者之间的等位基因和基因型频率比较.

主要成果:

与欧洲人相比,非欧洲人对CYP2C9,CYP2D6和CYP3A5的*1等位基因频率较高 (P <0.01).
欧洲人对CYP2C19和VKORC1的*1等位基因频率较高 (P <0.01).
至少在一个祖先组中,CYP2B6,CYP2D6,CYP2C9,CYP2C19和SLCO1B1的错误阴性估计超过了1%.

结论:

对于*1等位基因和*1/*1基因型存在祖先特定的频率,非欧洲人对某些基因的频率更高.
非欧洲和欧洲人口都面临假负PGx结果的风险.
扩大PGx面板上的等位基因覆盖面对减轻假阴性风险和提高药物遗传学测试公平性至关重要.

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