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

Abstract

The diversity of biological effects resulting from exposure to dioxin may reflect the ability of this environmental pollutant to alter gene expression by binding to the arylhydrocarbon receptor (AHR) gene and related genes. AHR function may be regulated by structural variations in AHR itself, in the AHR repressor (AHRR), in the AHR nuclear translocator (ARNT), or in AHR target molecules such as cytochrome P-4501A1 (CYP1A1) and glutathione S-transferase. Analysis of the genomic organization of AHRR revealed an open reading frame consisting of a 2094-bp mRNA encoded by ten exons. We found one novel polymorphism, a substitution of Ala by Pro at codon 185 (GCC to CCC), in exon 5 of the AHRR gene; among 108 healthy unrelated Japanese women, genotypes 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 previously published polymorphisms of ARNT (D511N) or the CYP1A1 promoter (G-469A and C-459T) in our subjects, suggesting that these polymorphisms are rare in the Japanese population. No association was found between uterine endometriosis and any polymorphisms in the AHRR, AHR, ARNT, or CYP1A1 genes analyzed in the present study.

The cytochrome P4501A1 gene polymorphisms and endometriosis: a meta-analysis

“…After the full-text evaluation, five articles were excluded with reasons for no available data (n = 1) [11], irrelevance to endometriosis (n = 1) [12], duplicate publications (n = 3) [13][14][15]. An article providing data for two different subgroups (Caucasian and Asian) was counted as two separate studies [6].…”

The aryl hydrocarbon receptor constitutively represses c-myc transcription in human mammary tumor cells

“…Therefore, a second approach to evaluating putative AhR repression of c-myc transcription was taken. An evolutionarily conserved AhRR has been described in several species (Mimura et al, 1999;Baba et al, 2001;Watanabe et al, 2001;Karchner et al, 2002;Korkalainen et al, 2004). The AhRR potently inhibits AhR-dependent CYP1A1 transcription by competing for the AhR binding partner ARNT and by blocking AhR-AhRE binding (Mimura et al, 1999;Karchner et al, 2002).…”

Polymorphisms and haplotypes of the gene encoding the estrogen-metabolizing CYP19 gene in Korean women: no association with advanced-stage endometriosis

“…There is increasing evidence that endometriosis is inherited as a complex genetic trait, implying that multiple gene loci interact with both each other and the environment to produce the phenotype disease (Kennedy 1997). Recent genetic studies have found an association between the development of endometriosis and the polymorphisms of several genes (Cramer et al 1996;Baranova et al 1997;Watanabe et al 2001;Chang et al 2002;Wieser et al 2002;Hur et al 2005), including the genes related to estrogen metabolism (Georgiou et al 1999;Kitawaki et al 2001;Kado et al 2002).…”