Glubb Dylan M, Dholakia Neepa, Innocenti Federico
Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina at Chapel Hill Chapel Hill, NC, USA.
Front Genet. 2012 Aug 14;3:153. doi: 10.3389/fgene.2012.00153. eCollection 2012.
Expression quantitative trait loci (eQTL) analysis can provide insights into the genetic regulation of gene expression at a genomic level and this information is proving extremely useful in many different areas of research. As a consequence of the role of the liver in drug metabolism and disposition, the study of eQTLs in primary human liver tissue could provide a foundation for pharmacogenomics. Thus far, four genome-wide eQTL studies have been performed using human livers. Many liver eQTLs have been found to be reproducible and a proportion of these may be specific to the liver. Already these data have been used to interpret and inform clinic genome-wide association studies, providing potential mechanistic evidence for clinical associations and identifying genes which may impact clinical phenotypes. However, the utility of liver eQTL data has not yet been fully explored or realized in pharmacogenomics. As further liver eQTL research is undertaken, the genetic regulation of gene expression will become much better characterized and this knowledge will create a rational basis for the prospective pharmacogenomic study of many drugs.
表达数量性状基因座(eQTL)分析能够在基因组水平上深入了解基因表达的遗传调控,并且这一信息在许多不同的研究领域中都证明极为有用。由于肝脏在药物代谢和处置中的作用,对原代人肝脏组织中的eQTL进行研究可为药物基因组学提供基础。迄今为止,已使用人类肝脏进行了四项全基因组eQTL研究。许多肝脏eQTL已被发现具有可重复性,其中一部分可能是肝脏特有的。这些数据已经被用于解释和指导临床全基因组关联研究,为临床关联提供潜在的机制证据,并识别可能影响临床表型的基因。然而,肝脏eQTL数据在药物基因组学中的效用尚未得到充分探索或实现。随着进一步开展肝脏eQTL研究,基因表达的遗传调控将得到更好的表征,并且这一知识将为许多药物的前瞻性药物基因组学研究创造合理的基础。