Use of CEPH and non-CEPH lymphoblast cell lines in pharmacogenetic studies

Use of CEPH and non-CEPH lymphoblast cell lines in pharmacogenetic studies
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DOI:
10.1517/14622416.6.3.303
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发表时间:
2005-04-01
期刊:
影响因子:
2.1
通讯作者:
Dolan, ME
Dolan, ME
中科院分区:
医学4区
文献类型:
--
作者:
Shukla, SJ;Dolan, ME

文献摘要

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药物基因组学研究的一个长期目标是根据患者的基因组序列设计个体化治疗,以最大限度地提高疗效并最大限度地减少药物不良反应。识别预测药物反应的遗传变异是具有挑战性的,因为药物反应不仅反映了靶细胞固有的特性,而且还反映了宿主代谢因素。目前用于研究基因型-表型相关性的一种模型涉及使用淋巴母细胞系(LCL)。这些细胞系已被用于鉴定影响对癌症、辐射、运输、细胞毒性的反应或易感性的遗传变异,以及全局基因表达的变异。LCL,特别是那些来自大谱系,是一个有价值的资源,用于确定候选基因,并有潜力的研究,许多相关的表型。本文重点介绍了利用人类多态性研究中心(CEPH)和非CEPH细胞系进行药物遗传学研究的研究,以及与这种方法相关的优点和缺点。
A long-term goal of pharmacogenomic research is the design of individualized therapy based on the genomic sequence of the patient in order to maximize response and minimize adverse drug reactions. Identifying genetic variants that predict drug response is challenging because drug responses reflect not only properties intrinsic to the target cell, but also host metabolic factors. One model that is currently being employed to study genotype-phenotype correlations involves the use of lymphoblastoid cell lines (LCLs). These cell lines have been used to identify genetic variation that influences response or susceptibility to cancer, radiation, transport, cytotoxicity, and variation in global gene expression. LCLs, particularly those derived from large pedigrees, are a valuable resource for identifying candidate genes and have potential for studies of many relevant phenotypes. This paper highlights studies that have utilized Centre d' Etude du Polymorphisme Humain (CEPH) and non-CEPH cell lines derived from humans for pharmacogenetic studies, and the advantages and disadvantages associated with this approach.