Variability of the human aryl hydrocarbon receptor nuclear translocator (ARNT) gene

The aryl hydrocarbon receptor nuclear translocator (ARNT) plays an essential role in vertebrate transcriptional regulation as the common subunit of transcriptionally active complexes like the aryl hydrocarbon receptor (AHR)/ARNT heterodimer and hypoxia-inducible factor 1, mediating cellular responses to certain xenobiotics and to hypoxia, respectively. A cohort of healthy Caucasian volunteers was screened for genetic variations of ARNT. Six polymorphic sites could be identified, a variation in a G-stretch upstream of the ATG translation start site, a frequent silent mutation (G567C), two polymorphic sites in intron 9, and two single nucleotide substitutions leading to amino acid exchanges, G1531A (D511N) and T1551G (D517E). The frequencies were 0.005 for the Asn-coding allele and for the Glu-coding allele, respectively, with no linkage between these two mutations. Although no significant correlation with activities of CYP1A2, which is under regulatory control of the AHR/ARNT transcription complex, could be established, metabolic or pathological phenotypes may be associated with these variations.