Higher frequency of genetic variants conferring increased risk for ADRs for commonly used drugs treating cancer, AIDS and tuberculosis in persons of African descent.
Higher frequency of genetic variants conferring increased risk for ADRs for commonly used drugs treating cancer, AIDS and tuberculosis in persons of African descent.
复制标题
DOI：
10.1038/tpj.2013.13
复制
发表时间：
2014-04
期刊：
影响因子：
--
通讯作者：
Canadian Pharmacogenomics Network for Drug Safety Consortium
中科院分区：
文献类型：
--
作者：
Aminkeng F;Ross CJ;Rassekh SR;Brunham LR;Sistonen J;Dube MP;Ibrahim M;Nyambo TB;Omar SA;Froment A;Bodo JM;Tishkoff S;Carleton BC;Hayden MR;Canadian Pharmacogenomics Network for Drug Safety Consortium
有临床证据表明不同种族人群之间的药物反应，治愈率和生存结局存在差异，但原因尚不清楚。关键药物反应和代谢基因中功能性遗传变异频率的差异可能显著影响不同人群中的药物反应差异。为了评估这一点，我们对1330名非洲（n = 372）和欧洲（n = 958）血统的个体进行了基因分型，在350个关键药物吸收、分布、代谢、消除和毒性基因中发现了4535个单核苷酸多态性。在非洲人和欧洲人之间以及在非洲人口之间观察到遗传变异分布的重要和显著差异。这些可能会转化为药物疗效和安全性方面的显著差异，以及在不同人群中达到预期治疗效果所需的剂量。我们的数据表明，在个性化医疗和护理中需要群体特异性遗传变异。
There is established clinical evidence for differences in drug response, cure rates and survival outcomes between different ethnic populations, but the causes are poorly understood. Differences in frequencies of functional genetic variants in key drug response and metabolism genes may significantly influence drug response differences in different populations. To assess this, we genotyped 1330 individuals of African (n = 372) and European (n = 958) descent for 4535 single-nucleotide polymorphisms in 350 key drug absorption, distribution, metabolism, elimination and toxicity genes. Important and remarkable differences in the distribution of genetic variants were observed between Africans and Europeans and among the African populations. These could translate into significant differences in drug efficacy and safety profiles, and also in the required dose to achieve the desired therapeutic effect in different populations. Our data points to the need for population-specific genetic variation in personalizing medicine and care.