Human arylhydrocarbon receptor repressor (AHRR) gene: genomic structure and analysis of polymorphism in endometriosis

The diversity of biological effects resulting from exposure to dioxin may r eflect the ability of this environmental pollutant to alter gene expression by binding to the arylhydrocarbon receptor (AHR) gene and related genes. A HR function may be regulated by structural variations in AHR itself, in the AHR repressor (AHRR), in the AHR nuclear translocator (ARNT), or in AHR ta rget molecules such as cytochrome P-4501A1 (CYP1A1) and glutathione S-trans ferase. Analysis of the genomic organization of AHRR revealed an open readi ng frame consisting of a 2094-bp mRNA encoded by ten exons. We found one no vel polymorphism, a substitution of Ala by Pro at codon 185 (GCC to CCC), i n exon 5 of the AHRR gene: among 108 healthy unrelated Japanese women, geno types Ala/Ala, Ala/Pro, and Pro/Pro were represented, respectively, by 20 ( 18.5%), 49 (45.4%), and 39 (36.1%) individuals. We did not detect previousl y published polymorphisms of ARNT (D511N) or the CYP1A1 promoter (G-469A an d C-459T) in our subjects, suggesting that these polymorphisms are rare in the Japanese population. No association was found between uterine endometri osis and any polymorphisms in the AHRR, AHR, ARNT, or CYP1A1 genes analyzed in the present study.