175
Views
18
CrossRef citations to date
0
Altmetric
Research Article

Regulatory Polymorphisms and their Contribution to Interindividual Differences in the Expression of Enzymes Influencing Drug and Toxicant Disposition

, , &
Pages 263-301 | Published online: 09 Oct 2008
 

Abstract

The unexpected paucity of human protein encoding genes suggested that polymorphisms altering gene expression might be more important than initially thought. From an evolutionary perspective, traits such as xenobiotic metabolism and transport that require a dynamic response to environmental changes would evolve more efficiently through variation in regulatory sequences versus coding variants. Such variation would be manifest as co-dominant traits and selection pressures would operate more efficiently because of their ability to impact fitness in the heterozygous state. Our current understanding of regulatory polymorphisms impacting drug disposition is reviewed including specific discussion regarding knowledge gaps and future research opportunities.

ABBREVIATIONS
ADH:=

Alcohol dehydrogenase

ALDH:=

Aldehyde dehydrogenase

ARP-1:=

Apoliprotein A regulatory protein

COUP-TF:=

Chicken ovalbumin upstream promoter-transcription factor

CYP:=

Cytochrome P450

EPHX:=

Epoxide hydrolase

FMO:=

Flavin-containing monooxygenase

GST:=

Glutathione S-transferase

MAF:=

Minor allele frequency

MPA:=

Mycophenolic acid

PXR:=

Pregnane-x-receptor

SLC6A4:=

Serotonin transporter

SN-38:=

7-ethyl-10-hydroxycamptothecin

SNP:=

Single nucleotide polymorphism

SSRI:=

Selective serotonin reuptake inhibitor

SULT:=

Sulfotransferase

TPMT:=

Thiopurine methyltransferase

UGT:=

UDP glucuronosyltransferase

VNTR:=

Variable number tandem repeat

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.