Phenotype-genotype analysis of CYP2C19 in Colombian mestizo individuals.
Phenotype-genotype analysis of CYP2C19 in Colombian mestizo individuals.
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DOI：
10.1186/1472-6904-7-6
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发表时间：
2007-07-11
期刊：
影响因子：
--
通讯作者：
Beltrán L
中科院分区：
文献类型：
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作者：
Isaza C;Henao J;Martínez JH;Sepúlveda Arias JC;Beltrán L
奥美拉唑通过肝细胞色素P450（CYP）2C 19酶代谢为5-羟基奥美拉唑。CYP 2C 19表现出遗传多态性，导致存在慢代谢型（PM）、中间代谢型（IM）和快代谢型（EM）。该酶的缺陷突变及其频率在不同种族之间发生变化;然而，尚未在哥伦比亚混血儿中研究CYP 2C 19基因的多态性。本研究的目的是评估哥伦比亚混血儿CYP 2C 19的基因型和表型状态，以便为该人群使用适当的药物治疗策略做出贡献。使用多重SNaPshot技术对189例受试者进行基因分型，44例受试者的亚组接受20 mg奥美拉唑，然后在3小时采集血液，通过HPLC测定奥美拉唑羟基化指数。83.6%、15.3%和1.1%的受试者的基因分型为EM、IM和PM。CYP 2C 29 *1和CYP 2C 19 *2等位基因频率分别为91.3%和8.7%，未发现 *3、*4、*5、*6和 *8等位基因，CYP 2C 19基因型与表型之间无差异。本研究中哥伦比亚混血儿中代谢不良者的频率（1.1%）与玻利维亚混血儿（1%）相似，但低于墨西哥裔美国人（3.2%）、西墨西哥人（6%）、高加索人（5%）和非洲裔美国人（5.4%）。这项研究的结果将是有用的药物剂量建议在哥伦比亚混血儿。
Omeprazole is metabolized by the hepatic cytochrome P450 (CYP) 2C19 enzyme to 5-hydroxyomeprazole. CYP2C19 exhibits genetic polymorphisms responsible for the presence of poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers (EMs). The defective mutations of the enzyme and their frequencies change between different ethnic groups; however, the polymorphism of the CYP2C19 gene has not been studied in Colombian mestizos. The aim of this study was to evaluate the genotype and phenotype status of CYP2C19 in Colombian mestizos, in order to contribute to the use of appropriate strategies of drug therapy for this population. 189 subjects were genotyped using the multiplex SNaPshot technique and a subgroup of 44 individuals received 20 mg of omeprazole followed by blood collection at 3 hours to determine the omeprazole hydroxylation index by HPLC. 83.6%, 15.3% and 1.1% of the subjects were genotyped as EMs, IMs and PMs, respectively. The frequencies of the CYP2C29*1 and CYP2C19*2 alleles were 91.3% and 8.7% respectively whereas the *3, *4, *5, *6 and *8 alleles were not found. No discrepancies were found between the genotype and phenotype of CYP2C19. The frequency of poor metabolizers (1.1%) in the Colombian mestizos included in this study is similar to that in Bolivian mestizos (1%) but lower than in Mexican-Americans (3.2%), West Mexicans (6%), Caucasians (5%) and African Americans (5.4%). The results of this study will be useful for drug dosage recommendations in Colombian mestizos.