Identification of a novel variant CYP2C9 allele in Chinese
Identification of a novel variant CYP2C9 allele in Chinese
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DOI：
10.1097/01.fpc.0000114749.08559.e4
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发表时间：
2004-07-01
期刊：
影响因子：
--
通讯作者：
Zhong, DF
中科院分区：
文献类型：
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作者：
Si, DY;Guo, YJ;Zhong, DF
目的细胞色素P450（CYP 2C 9）代谢目前临床使用的药物的16%，包括氯诺昔康和甲苯磺丁脲。在CYP 2C 9基因的SNPs已越来越多地被认为是代谢表型的决定因素，underlies interindividual and ethnic differences.Methods本研究的重点是中国弱代谢者（PM）的表观基因型（CYP 2C 9 *1/CYP 2C 9 *3）不同意他的PM表型氯诺昔康和甲苯磺丁脲。结果该弱代谢型家系的CYP 2C 9基因型分析显示，该家系的CYP 2C 9 *3基因位于不同的等位基因上，外显子2的T269 C颠换导致编码蛋白的Leu 90 Pro替换，而外显子2的T269 C颠换导致编码蛋白的Leu 90 Pro替换。因此，该受试者的PM状态可归因于其为CYP 2C 9 T269 C等位基因和CYP 2C 9 *3杂合子。在147个无关的中国男性的频率分析表明，约2%的中国人口携带等位基因。结论这项研究表明，这种新的CYP 2C 9等位基因与降低血浆清除率的药物是CYP 2C 9的底物。(C)2004年利平科特威廉姆斯威尔金斯。
Objectives Cytochrome P450 (CYP) 2C9 metabolizes about 16% of drugs in current clinical use, including lornoxicam and tolbutamide. SNPs in the CYP2C9 gene have increasingly been recognized as determinants of the metabolic phenotype that underlies interindividual and ethnic differences.Methods The present study focused on a Chinese poor metabolizer (PM) whose apparent genotype (CYP2C9*1/CYP2C9*3) did not agree with his PM phenotype for both lornoxicam and tolbutamide. By sequencing his CYP2C9 gene, we identified a new variant CYP2C9 allele involving a T269C transversion in exon 2 that leads to a Leu90Pro substitution in the encoded protein.Results The CYP2C9 genotype analysis in the family of the poor metabolizer showed the new axon 2 change and CYP2C9*3 occurred on different alleles. Thus, the PM status of this subject could be attributed to his being heterozygous for the CYP2C9 T269C allele together with the CYP2C9*3. Frequency analysis in 147 unrelated Chinese males indicated approximately 2% of the Chinese population carry the allele.Conclusion This study suggests that this novel CYP2C9 allele was correlated with reduced plasma clearance of drugs that are substrates for CYP2C9. (C) 2004 Lippincott Williams Wilkins.