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Clinical significance of the cytochrome P450 2C19 genetic polymorphism.细胞色素P450 2C19基因多态性的临床意义
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Molecular basis of ethnic differences in drug disposition and response.药物处置和反应中种族差异的分子基础。
Annu Rev Pharmacol Toxicol. 2001;41:815-50. doi: 10.1146/annurev.pharmtox.41.1.815.
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A novel transversion in the intron 5 donor splice junction of CYP2C19 and a sequence polymorphism in exon 3 contribute to the poor metabolizer phenotype for the anticonvulsant drug S-mephenytoin.
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Frequencies of the defective CYP2C19 alleles responsible for the mephenytoin poor metabolizer phenotype in various Oriental, Caucasian, Saudi Arabian and American black populations.在不同的东方、高加索、沙特阿拉伯和美国黑人人群中,导致美芬妥英慢代谢者表型的CYP2C19缺陷等位基因的频率。
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Genetic tests which identify the principal defects in CYP2C19 responsible for the polymorphism in mephenytoin metabolism.
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The hydroxylation of omeprazole correlates with S-mephenytoin metabolism: a population study.奥美拉唑的羟基化与S-美芬妥英代谢相关:一项群体研究。
Clin Pharmacol Ther. 1995 Jun;57(6):662-9. doi: 10.1016/0009-9236(95)90229-5.
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马来西亚健康人群细胞色素P450 2C19的基因多态性

Genetic polymorphism of cytochrome P450 2C19 in healthy Malaysian subjects.

作者信息

Pang Y S, Wong L P, Lee T C, Mustafa A M, Mohamed Z, Lang Chim C

机构信息

Faculty of Medicine, University of Malaya, Kuala Lumpar, Malaysia.

出版信息

Br J Clin Pharmacol. 2004 Sep;58(3):332-5. doi: 10.1111/j.1365-2125.2004.02144.x.

DOI:10.1111/j.1365-2125.2004.02144.x
PMID:15327595
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1884559/
Abstract

AIMS

Impaired S-mephenytoin 4'-hydroxylation is a well-described genetic polymorphism affecting drug metabolism in humans. Although ethnic differences in its distribution of polymorphism has been described, it is not known whether there is an ethnic heterogeneity of the structure and expression of the CYP2C19 enzyme in the Malaysian population.

METHODS

Study subjects were 142 healthy, unrelated Malaysians aged 18-29 years. Baseline omeprazole and 2-h postingestion omeprazole and 5'-hydroxyomeprazole concentrations were measured for CYP2C19 phenotype determination. Identification of CYP2C19 genotypes was performed with the use of polymerase chain reaction.

RESULTS

Phenotyping of CYP2C19 revealed that the prevalence of poor metabolizers (PMs) in the Malaysian population was 14.1%, whereas prevalence of PMs in genotyping was 12.6%. The PM genotypic prevalence rate was 5.6% in Malays, 19.1% in Chinese and 10.0% in Indian subjects. There were significant differences in PM genotypic prevalence rates among the three primary ethnic groups (P < or = 0.05).

CONCLUSIONS

Phenotyping and genotyping revealed significant differences in the prevalence rates among the three ethnic groups in Malaysia, with Chinese recording highest prevalence.

摘要

目的

S-美芬妥英4'-羟化受损是一种已被充分描述的影响人类药物代谢的基因多态性。尽管已经描述了其多态性分布的种族差异,但尚不清楚马来西亚人群中CYP2C19酶的结构和表达是否存在种族异质性。

方法

研究对象为142名年龄在18至29岁之间的健康、无亲缘关系的马来西亚人。测量基线奥美拉唑以及摄入后2小时的奥美拉唑和5'-羟基奥美拉唑浓度以确定CYP2C19表型。使用聚合酶链反应进行CYP2C19基因型鉴定。

结果

CYP2C19表型分析显示,马来西亚人群中代谢缓慢者(PMs)的患病率为14.1%,而基因分型中PMs的患病率为12.6%。马来人的PM基因型患病率为5.6%,华人中为19.1%,印度受试者中为10.0%。三个主要种族群体的PM基因型患病率存在显著差异(P≤0.05)。

结论

表型分析和基因分型显示,马来西亚三个种族群体的患病率存在显著差异,华人的患病率最高。