Pharmacogenomic assessment of carboxylesterases 1 and 2
Pharmacogenomic assessment of carboxylesterases 1 and 2
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DOI：
10.1016/j.ygeno.2004.07.008
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发表时间：
2004-10-01
期刊：
影响因子：
4.4
通讯作者：
McLeod, HL
中科院分区：
文献类型：
--
作者：
Marsh, S;Xiao, M;McLeod, HL
人羧酸酯酶1和2（CES 1和CES 2）催化许多外源化合物的水解。羧酸酯酶序列的改变可能导致药物失活和前药活化的变异性。我们在多个人群（n = 120）中对CES 1和CES 2进行了重新测序，以确定单核苷酸多态性，并在健康的欧洲和非洲个体（n = 190）中证实了新的SNP。在至少一个群体中，在CES 1（每300 bp I）和CES 2（每630 bp I）中发现了16个SNP。等位基因频率和估计的单倍型频率在非洲和欧洲人群之间差异显着。没有发现CES 1或CES 2中的SNP与正常结肠粘膜中的RNA表达相关;然而，CES 2中的内含子SNP（IVS 1088）与结肠直肠肿瘤中CES 2 mRNA表达降低相关。本研究中描述的新的多态性的功能分析，现在有必要确定药物代谢中的假定作用。(C)2004年爱思唯尔公司All rights reserved.
Human carboxylesterases 1 and 2 (CES1 and CES2) catalyze the hydrolysis of many exogenous compounds. Alterations in carboxylesterase sequences could lead to variability in both the inactivation of drugs and the activation of prodrugs. We resequenced CES1 and CES2 in multiple populations (n = 120) to identify single-nucleotide polymorphisms and confirmed the novel SNPs in healthy European and African individuals (n = 190). Sixteen SNPs were found in CES1 (I per 300 bp) and I I in CES2 (I per 630 bp) in at least one population. Allele frequencies and estimated haplotype frequencies varied significantly between African and European populations. No association between SNPs in CES1 or CES2 was found with respect to RNA expression in normal colonic mucosa; however, an intronic SNP (IVS1088) in CES2 was associated with reduced CES2 mRNA expression in colorectal tumors. Functional analysis of the novel polymorphisms described in this study is now warranted to identify putative roles in drug metabolism. (C) 2004 Elsevier Inc. All rights reserved.