Jin Ye, Zhang Shuquan, Hu Pei, Zheng Xin, Guan Xiaoduo, Chen Rui, Zhang Shuyang
State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Front Pharmacol. 2022 Aug 30;13:940510. doi: 10.3389/fphar.2022.940510. eCollection 2022.
The variant is the second or third frequent reduced function allele in Chinese with a frequency of around 3-4%, while it is the major reduced function allele in Indians, Saudi Arabians and Caucasians with frequencies of around 10-20%. The present study was designed to explore the impact of on the metabolic activity of using phenotyping methods in urine, plasma, and saliva. We used dextromethorphan as the probe drug to analyze the phenotypes of 87 subjects with / ( = 22), / ( = 33), / ( = 4), / ( = 5), / ( = 3), / ( = 16), and / ( = 4) for . The ratio of parent drug to metabolite in 3 h saliva, 3 h plasma, and in 0-3 h urine was considered the metabolic ratio (MR). The allele had substantial impact on the metabolic activity of regardless of the urinary, plasma, or salivary phenotyping method used. In subjects with (or )/(or ), (or )/, / and / (all < 0.001), the salivary, plasma, or urinary MR value increased. The MRs in saliva, plasma, and urine displayed high correlations. The activity score system or the consensus activity score system, instead of the traditional phenotype classification, could predict the enzyme activity more accurately. had similar or more impact on the enzyme activity as compared with . Assigning a score of 0.5 and assigning a score of 0.25 according to the consensus AS system should be reconsidered.
该变体是中国人中第二或第三常见的功能降低等位基因，频率约为3%-4%，而在印度人、沙特阿拉伯人和高加索人中，它是主要的功能降低等位基因，频率约为10%-20%。本研究旨在通过尿液、血浆和唾液的表型分析方法，探讨其对代谢活性的影响。我们使用右美沙芬作为探针药物，分析了87名具有/（=22）、/（=33）、/（=4）、/（=5）、/（=3）、/（=16）和/（=4）基因型受试者的表型。3小时唾液、3小时血浆和0-3小时尿液中母体药物与代谢物的比率被视为代谢率（MR）。无论使用尿液、血浆还是唾液表型分析方法，等位基因对的代谢活性都有显著影响。在具有（或）/（或）、（或）/、/和/（均<0.001）的受试者中，唾液、血浆或尿液MR值升高。唾液、血浆和尿液中的MR显示出高度相关性。活性评分系统或共识活性评分系统，而非传统的表型分类，能够更准确地预测酶活性。与相比，对酶活性具有相似或更大的影响。根据共识AS系统，将的评分设为0.5，将的评分设为0.25，这一点应重新考虑。
