Drug Metabolism and Pharmacokinetics
Online ISSN : 1880-0920
Print ISSN : 1347-4367
ISSN-L : 1347-4367
Single nucleotide polymorphisms in the human aryl hydrocarbon receptor nuclear translocator (ARNT) gene
Jonathan D. UrbanRobert A. BudinskyJ. Craig Rowlands
Author information
JOURNAL FREE ACCESS Advance online publication

Article ID: DMPK-11-SC-031


  Species' variation(s) in gene homologues can result in differences among species in their quantitative and qualitative susceptibility and responsiveness to environmental contaminants. In the case of dioxin-like compounds (DLCs), it has been hypothesized that single nucleotide polymorphisms (SNPs) in genes associated with aryl hydrocarbon receptor (AHR)-regulated pathways may result in greater susceptibility to DLC toxicity. A key step in the activation of aryl hydrocarbon receptor (AHR) involves heterodimerization with the AHR nuclear translocator (ARNT) protein before binding to its DNA response element. The objective of this study was to identify single nucleotide polymorphisms (SNPs) in the human ARNT gene that could potentially affect the sensitivity of AHR-dependent gene transcription. Results from DNA sequencing of 101 human samples demonstrated the presence of five unique SNPs at the ARNT locus, including three non-synonymous SNPs, of which two were novel: V304M and T462A. The genetic frequencies of the non-synonymous SNPs were very low (≤ 0.02), and the novel SNPs occurred in the Per-ARNT-Sim (PAS) functional domain. In silico analysis indicated that V304M was the only SNP identified in the current population with the potential to significantly alter ARNT protein function. Our findings indicated a very limited occurrence of SNPs with predicted functional consequence in key domains of the human ARNT.

Information related to the author

This article cannot obtain the latest cited-by information.

© 2011 by The Japanese Society for the Study of Xenobiotics