Pharmacogenomics, ancestry and clinical decision making for global populations
Pharmacogenomics, ancestry and clinical decision making for global populations
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DOI：
10.1038/tpj.2013.24
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发表时间：
2014-06-01
影响因子：
2.8
通讯作者：
Rotimi, C. N.
中科院分区：
文献类型：
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作者：
Ramos, E.;Doumatey, A.;Rotimi, C. N.
已知药物反应和药物不良反应的药物遗传学相关标志物在人群中的频率不同。我们研究了19个人群（n=1478）中涉及药物吸收、分布、代谢和排泄（ADME）的212个基因中1156个遗传变异（包括42个临床可行的变异）的次要等位基因频率（MAF）、遗传多样性（F-ST）和群体结构。在这些ADME变异体中存在广泛的人群分化，反映在平均MAF（Delta MAF）和F-ST的范围内。在非洲血统人群中观察到最大的平均Delta MAF（0.10）和东亚血统人群中最小的平均AMAF（0.04）。MAF范围很广，例如，从影响华法林剂量的单核苷酸多态性（SNP）rs 9923231的0.93到与卡培他滨代谢相关的SNP rs3918290的0.01。ADME遗传变异在大陆群体之间和群体内部显示出显著的差异。扩大药物基因组学研究的范围，使其包括多个全球人群，可以改善临床转化的证据基础，使所有人受益。
Pharmacogenomically relevant markers of drug response and adverse drug reactions are known to vary in frequency across populations. We examined minor allele frequencies (MAFs), genetic diversity (F-ST) and population structure of 1156 genetic variants (including 42 clinically actionable variants) in 212 genes involved in drug absorption, distribution, metabolism and excretion (ADME) in 19 populations (n=1478). There was wide population differentiation in these ADME variants, reflected in the range of mean MAF (Delta MAF) and F-ST. The largest mean Delta MAF was observed in African ancestry populations (0.10) and the smallest mean AMAF in East Asian ancestry populations (0.04). MAFs ranged widely, for example, from 0.93 for single-nucleotide polymorphism (SNP) rs9923231, which influences warfarin dosing to 0.01 for SNP rs3918290 associated with capecitabine metabolism. ADME genetic variants show marked variation between and within continental groupings of populations. Enlarging the scope of pharmacogenomics research to include multiple global populations can improve the evidence base for clinical translation to benefit all peoples.