CYP2D6 Phenotyping Using Urine, Plasma, and Saliva Metabolic Ratios to Assess the Impact of CYP2D6(∗)10 on Interindividual Variation in a Chinese Population.
CYP2D6 Phenotyping Using Urine, Plasma, and Saliva Metabolic Ratios to Assess the Impact of CYP2D6(∗)10 on Interindividual Variation in a Chinese Population.
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使用尿液、血浆和唾液代谢比率进行 CYP2D6 表型分析，评估 CYP2D610 对中国人群个体差异的影响
DOI：
10.3389/fphar.2017.00239
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发表时间：
2017
影响因子：
5.6
通讯作者：
Hu P
中科院分区：
文献类型：
--
作者：
Chen R;Zheng X;Hu P
目的：亚洲人群中功能降低等位基因 CYP2D6*10 的出现频率约为 40-60%，而白种人人群中这一比例为 1-2%。具有 CYP2D6*10 变异体的受试者中广泛的 CYP2D6 酶活性是临床实践中的一个大问题。在大量亚洲人群中尚未报道测量一个 CYP2D6*10 等位基因或两个 CYP2D6*10 等位基因对 CYP2D6 酶活性影响的定量分析。方法：通过聚合酶链反应和直接DNA测序对421名健康中国受试者进行CYP2D6基因分型。使用右美沙芬作为探针药物，对总共 235 名 CYP2D6*1/*1 (n = 22)、CYP2D6*1/*10 (n = 93)、CYP2D6*10/*10 (n = 85) 和 CYP2D6*5/*10 (n = 35) 受试者进行 CYP2D6 表型分析。代谢比 (MR) 计算为每种样品类型 0-3 小时尿液、3 小时血浆和 3 小时唾液中母药与代谢物的比率。结果：CYP2D6*1/*1、*1/*10、*10/*10 和*5/*10 受试者的尿液、血浆或唾液 MR 依次升高（均 P < 0.001）。在正常代谢组中，纯合子 CYP2D6*10/*10 比杂合子 CYP2D6*1/*10 进一步降低了 CYP2D6 酶活性。尿液、血浆和唾液 MR 高度相关。结论：正常代谢组需要更详细的分类。与将多个基因型分组为单个表型组相比，活性评分系统可以更准确地预测酶活性。单点血浆样本和唾液样本可用作替代表型分析方法，以方便临床。
Purpose: Asian populations have around 40–60% frequency of reduced function allele CYP2D6∗10 compared to 1–2% in Caucasian populations. The wide range of CYP2D6 enzyme activities in subjects with the CYP2D6∗10 variant is a big concern for clinical practice. The quantitative analysis measuring the impact of CYP2D6 enzyme activity as a result of one CYP2D6∗10 allele or two CYP2D6∗10 alleles has not been reported in large Asian populations. Methods: A total of 421 healthy Chinese subjects were genotyped for CYP2D6 by polymerase chain reaction and direct DNA sequencing. A total of 235 subjects with CYP2D6∗1/∗1 (n = 22), CYP2D6∗1/∗10 (n = 93), CYP2D6∗10/∗10 (n = 85), and CYP2D6∗5/∗10 (n = 35) were phenotyped for CYP2D6 using dextromethorphan as the probe drug. Metabolic ratios (MR) were calculated as the ratio of parent drug to metabolite in 0–3 h urine, 3 h plasma, and 3 h saliva for each sample type. Results: The urinary, plasma, or salivary MRs increased successively in subjects with CYP2D6∗1/∗1, ∗1/∗10, ∗10/∗10, and ∗5/∗10 (all P < 0.001). In the normal metabolizer group, homozygous CYP2D6∗10/∗10 decreased the CYP2D6 enzyme activity further than heterozygous CYP2D6∗1/∗10. Urinary, plasma, and salivary MRs were highly correlated. Conclusion: The normal metabolizer group calls for a more detailed classification. The activity score system could more accurately predict enzyme activity than by grouping a number of genotypes into a single phenotype group. Single-point plasma samples and saliva samples could be used as alternative phenotyping methods for clinical convenience.