The CYP2D6 activity score: Translating genotype information into a qualitative measure of phenotype
The CYP2D6 activity score: Translating genotype information into a qualitative measure of phenotype
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DOI：
10.1038/sj.clpt.6100406
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发表时间：
2008-02-01
影响因子：
6.7
通讯作者：
Leeder, J. S.
中科院分区：
文献类型：
--
作者：
Gaedigk, A.;Simon, S. D.;Leeder, J. S.
考虑到越来越多的等位基因及其活性范围，从基因型推断CYP 2D 6表型越来越具有挑战性。这种复杂性对转化研究提出了挑战，其中基因分型被认为是个性化药物治疗的工具。为了简化基因型解释和提高表型预测，我们评估了“活性评分”（AS）系统的实用性。在672例主要为高加索人和非裔美国人的受试者中，对超过25种CYP 2D 6等位基因变体进行了基因分型。使用线性回归和聚类方法评估基因型和AS使用CYP 2D 6探针底物美沙芬准确预测表型的能力。如果考虑种族因素，以每个AS组的概率给出的表型预测是最准确的;在含有CYP 2D 6 *2等位基因的基因型受试者中，非裔美国人的CYP 2D 6活性显著低于白人。AS工具保证对CYP 2D 6底物和其他种族人群进行进一步的前瞻性评价。
Inferring CYP2D6 phenotype from genotype is increasingly challenging, considering the growing number of alleles and their range of activity. This complexity poses a challenge in translational research where genotyping is being considered as a tool to personalize drug therapy. To simplify genotype interpretation and improve phenotype prediction, we evaluated the utility of an "activity score'' ( AS) system. Over 25 CYP2D6 allelic variants were genotyped in 672 subjects of primarily Caucasian and African-American heritage. The ability of genotype and AS to accurately predict phenotype using the CYP2D6 probe substrate dextromethorphan was evaluated using linear regression and clustering methods. Phenotype prediction, given as a probability for each AS group, was most accurate if ethnicity was considered; among subjects with genotypes containing a CYP2D6*2 allele, CYP2D6 activity was significantly slower in African Americans compared to Caucasians. The AS tool warrants further prospective evaluation for CYP2D6 substrates and in additional ethnic populations.