Lamba Jatinder K
St Jude Children's Research Hospital, Department of Pharmaceutical Sciences, 332 North Lauderdale Street, Memphis, TN 38105, USA.
Pharmacogenomics. 2008 Jan;9(1):71-83. doi: 10.2217/14622416.9.1.71.
The constitutive androstane receptor (CAR), a member of the NR1I group of nuclear hormone receptors, has been implicated in regulating the expression of genes that are critical in xenobiotic and endobiotic metabolism, uptake and elimination as well as genes involved in various other physiological processes. Hence, functional variation in CAR associated with its expression and/or activity can influence the transcriptional activation of its target genes and could contribute to the observed variation in drug response and toxicity. Moreover, coadministration of agents that are also CAR activators contributes to clinically relevant drug-drug interactions in patients receiving certain combination therapies. This review will discuss the functional significance of known genetic variants in CAR and the most common alternatively spliced isoforms of CAR. We will also discuss the influence of gender and ethnicity on CAR and its target genes. Although genetic polymorphisms in CAR may have an indirect effect on drug disposition, understanding the association of genetic polymorphisms in CAR with the expression of its target genes might help us to better understand the molecular mechanisms underlying the interindividual variation in drug disposition in addition to drug-drug interactions.
组成型雄烷受体（CAR）是核激素受体NR1I家族的成员之一，参与调控对外源性和内源性物质代谢、摄取及清除起关键作用的基因的表达，以及参与各种其他生理过程的基因的表达。因此，与CAR表达和/或活性相关的功能变异可影响其靶基因的转录激活，并可能导致观察到的药物反应和毒性差异。此外，同时给予也是CAR激活剂的药物会导致接受某些联合治疗的患者出现临床相关的药物-药物相互作用。本综述将讨论CAR中已知基因变异和最常见的可变剪接异构体的功能意义。我们还将讨论性别和种族对CAR及其靶基因的影响。尽管CAR中的基因多态性可能对药物处置有间接影响，但了解CAR基因多态性与其靶基因表达之间的关联，除有助于理解药物-药物相互作用外，还可能帮助我们更好地理解个体间药物处置差异背后的分子机制。
