Sim Sarah C, Ingelman-Sundberg Magnus
Division of Molecular Toxicology, IMM, Karolinska Institutet, Stockholm, Sweden.
Methods Mol Biol. 2006;320:183-191. doi: 10.1385/1-59259-998-2:183.
Interindividual variability in xenobiotic metabolism and drug response is extensive. Genetic factors are predicted to account for 15-30% of this variability in general, but for certain drugs the genetic factor is the major determinant for outcome of drug therapy. Of particular importance for drug metabolism, drug response, and adverse drug reactions are the cytochrome P450 (CYP) enzymes, many of which are polymorphic. An essential basis for research and applications regarding interindividual variability in xenobiotic metabolism and toxicity by polymorphic CYPs is to have a common nomenclature for genetic variants and a system that allows researchers to be rapidly updated within the field. Since 1999 this has been achieved by the operation of the Human Cytochrome P450 Allele Nomenclature Committee Web site ( http://www.imm.ki.se/CYPalleles/ ), where novel allelic variants are published after peer review. Currently, this Web site covers the nomenclature for polymorphic alleles of 22 CYP isoforms including more than 200 functionally different variants. Each CYP has its own Web page, which lists the alleles with their nucleotide changes, their functional consequences, and links to publications where the allele has been identified and characterized. The CYP allele Web site offers a rapid on-line publication of new alleles, provides an overview of peer-reviewed data, and serves as a form of quality control on research on new alleles.
异生物代谢和药物反应的个体间差异非常大。一般来说,遗传因素预计占这种差异的15%至30%,但对于某些药物而言,遗传因素是药物治疗结果的主要决定因素。细胞色素P450(CYP)酶对于药物代谢、药物反应和药物不良反应尤为重要,其中许多酶具有多态性。关于多态性CYP在异生物代谢和毒性方面个体间差异的研究和应用的一个重要基础是要有一个通用的遗传变异命名法和一个能让研究人员在该领域内迅速获取最新信息的系统。自1999年以来,通过人类细胞色素P4-50等位基因命名委员会网站(http://www.imm.ki.se/CYPalleles/)的运作实现了这一点,新的等位基因变异在同行评审后发布。目前,该网站涵盖了22种CYP同工型多态性等位基因的命名法,包括200多个功能不同的变异。每个CYP都有自己的网页,列出了等位基因及其核苷酸变化、功能后果,以及指向已鉴定和表征该等位基因的出版物的链接。CYP等位基因网站提供新等位基因的快速在线发布,提供同行评审数据的概述,并作为对新等位基因研究的一种质量控制形式。