Drug Metabolism and Pharmacokinetics
Online ISSN : 1880-0920
Print ISSN : 1347-4367
ISSN-L : 1347-4367
An evaluation of single nucleotide polymorphisms in the human aryl hydrocarbon receptor-interacting protein (AIP) gene
J. Craig RowlandsJonathan D. UrbanDaniele Staskal WikoffRobert A. Budinsky
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JOURNALS FREE ACCESS Advance online publication

Article ID: DMPK-11-SC-013


  The human aryl hydrocarbon receptor (AHR) is a protein for which there is little evidence of polymorphic variability of functional consequence. It has been hypothesized that potential variability in dioxin sensitivity may be due to polymorphisms in AHR-associated proteins, such as the human AHR interacting protein (AIP). There are limited data on AIP single nucleotide polymorphisms (SNPs) with potential functional consequences in the sequences. We sequenced 103 human DNA samples within the open reading frames of the AIP locus using samples from six ethnic populations to further characterize AIP SNPs. Eight exonic SNPs were identified at the AIP locus, including three novel SNPs: T48T, L212L, and V302V. Combined with prior reports, there are now a total of 14 exonic SNPs that have been identified within AIP. Of these, six are non-synonymous and are therefore of potential functional importance, though only two of these (Q228K and A276V) were detected in the current study. The functional consequences of Q228K and A276V are unknown, although functional evidence from AIP SNPs associated with congenital pituitary tumors suggest that such amino acid changes are likely to have no effect or decrease, rather than increase, sensitivity to dioxins. To date, no non-synonymous SNPs have been detected in the AHR-binding region of AIP.

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© 2011 by The Japanese Society for the Study of Xenobiotics