Staskal-Wikoff D, Budinsky R, Rowlands JC. 2011. Single nucleotide polymorphisms in the human aryl hydrocarbon receptor interacting protein (AIP) gene from six ethnic populations. Presented at the Society of Toxicology’s 50th Annual Meeting, March 6-10, Washington, D.C.
The biological effects of dioxin-like chemicals (DLCs) involve initial binding to and activation of the aryl hydrocarbon receptor (AHR). The human AHR interacting protein (AIP) is a chaperone protein that complexes with AHR, allowing for AHR ligand-binding complex stabilization. It also interacts with AHR and heat shock protein 90 (HSP90) to form a ligand-free AHR complex that prevents ubiquitination and limits protein degradation. Thus the presence of single amino acid polymorphisms at key functional domains in the AIP protein could affect AHR protein integrity and/or signaling. The objective of this study was to screen 103 human DNA samples from six ethnic populations for single nucleotide polymorphisms (SNPs) within the AIP gene that could potentially affect the sensitivity of the AHR response pathway. Of the 103 samples evaluated, 42 samples had at least one SNP, 12 samples had two SNPs, while one sample had three SNPs. Eight unique exonic SNPs were identified in the dataset. Three AIP SNPs had not been described previously in the literature or public databases, though these all resulted in synonymous substitutions. Two non-synonymous SNPs were identified; both were found in the African American population samples, and one was found in the Mexican group. One of these (A276V) is located in a defined functional region [the third tetratricopeptide repeats (TPR 3) domain], while the other (Q228R) was present between the TPR 1 and TPR 2 domains. Prior evidence suggests that a single point mutation within AIP TPR region can negatively affect AIP-protein binding, which could potentially disrupt AIP-HSP90 binding and compromise AHR protein integrity and cellular localization. Although this study found limited evidence of AIP SNPs of functional consequence, the results suggest that one or two AIP SNPs could result in decreased sensitivity to DLC exposures. Further investigation of the impact of these AIP SNPs on AHR signaling is warranted.