title: Genetic association of aromatic hydrocarbon receptor (AHR) and cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) polymorphisms with dioxin blood concentrations among pregnant Japanese women.
abstract: Dioxins are metabolized by cytochrome P450, family 1 (CYP1) via the aromatic hydrocarbon receptor (AHR). We determined whether different blood dioxin concentrations are associated with polymorphisms in AHR (dbSNP ID: rs2066853), AHR repressor (AHRR; rs2292596), CYP1 subfamily A polypeptide 1 (CYP1A1; rs4646903 and rs1048963), CYP1 subfamily A polypeptide 2 (CYP1A2; rs762551), and CYP1 subfamily B polypeptide 1 (CYP1B1; rs1056836) in pregnant Japanese women. These six polymorphisms were detected in 421 healthy pregnant Japanese women. Differences in dioxin exposure concentrations in maternal blood among the genotypes were investigated. Comparisons among the GG, GA, and AA genotypes of AHR showed a significant difference (genotype model: P=0.016 for the mono-ortho polychlorinated biphenyl concentrations and toxicity equivalence quantities [TEQs]). Second, we found a significant association with the dominant genotype model ([TT+TC] vs. CC: P=0.048 for the polychlorinated dibenzo-p-dioxin TEQs; P=0.035 for polychlorinated dibenzofuran TEQs) of CYP1A1 (rs4646903). No significant differences were found among blood dioxin concentrations and polymorphisms in AHRR, CYP1A1 (rs1048963), CYP1A2, and CYP1B1. Thus, polymorphisms in AHR and CYP1A1 (rs4646903) were associated with maternal dioxin concentrations. However, differences in blood dioxin concentrations were relatively low.
authors.affiliation: Department of Public Health Sciences, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Hokkaido, Japan.
authors.forename: Sumitaka
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Sata
authors.forename: Seiko
authors.initials: S
authors.lastname: Sasaki
authors.forename: Susumu
authors.initials: S
authors.lastname: Ban
authors.forename: Chihiro
authors.initials: C
authors.lastname: Miyashita
authors.forename: Emiko
authors.initials: E
authors.lastname: Okada
authors.forename: Mariko
authors.initials: M
authors.lastname: Limpar
authors.forename: Eiji
authors.initials: E
authors.lastname: Yoshioka
authors.forename: Jumboku
authors.initials: J
authors.lastname: Kajiwara
authors.forename: Takashi
authors.initials: T
authors.lastname: Todaka
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Saijo
authors.forename: Reiko
authors.initials: R
authors.lastname: Kishi
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004147:Dioxins / Q000097:blood* / Q000378:metabolism; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D005838:Genotype; D006801:Humans; D007564:Japan; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011247:Pregnancy; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*
chemical_list: D004147:Dioxins; D018336:Receptors, Aryl Hydrocarbon; D019363:Cytochrome P-450 CYP1A1