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 |
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| Authors: | Sumitaka Kobayashi Fumihiro Sata Seiko Sasaki Susumu Ban Chihiro Miyashita Emiko Okada Mariko Limpar Eiji Yoshioka Jumboku Kajiwara Takashi Todaka Yasuaki Saijo Reiko Kishi |
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| Affiliation: | 1. Department of Public Health Sciences, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Hokkaido, Japan;2. Department of Environmental Health, National Institute of Public Health, 2-3-6 Minami, Wako 351-0197, Saitama, Japan;3. Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3, Minami-Tamagaki-cho, Suzuka 513-8670, Mie, Japan;4. Center for Environmental and Health Sciences, Hokkaido University, North 12, West 7, Kita-ku, Sapporo 060-0812, Hokkaido, Japan;5. Department of Health Sciences, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa 078-8510, Hokkaido, Japan;6. Fukuoka Institute of Health and Environmental Sciences, Mukaizano 39, Dazaifu 818-0135, Fukuoka, Japan;g Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Fukuoka, Japan |
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| 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. |
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| Keywords: | PCDD, polychlorinated dibenzo-p-dioxin PCDF, polychlorinated dibenzofuran PCB, polychlorinated biphenyl TEQ, toxicity equivalence quantity AHR, aromatic hydrocarbon receptor TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin CYP1A1, cytochrome P450, family 1, subfamily A, polypeptide 1 CYP1A2, cytochrome P450, family 1, subfamily A, polypeptide 2 CYP1B1, cytochrome P450, family 1, subfamily B, polypeptide 1 AHRR, aromatic hydrocarbon receptor repressor CYP, cytochrome P450 GSTT1, glutathione S-transferase θ1 GSTM1, glutathione S-transferase μ1 HexCB, Hexachlorinated biphenyl PenCB, Pentachlorinated biphenyl TEF, toxicity equivalence factor SNPs, single-nucleotide polymorphisms PenCB, pentachlorinated biphenyl E, 217β-estradiol E1, estrone 2-OH-E, 22-hydroxyestradiol 4-OH-E, 24-hydroxyestradiol ERα, estrogen receptor α TSH, thyroid-stimulating hormone TSHβ, thyroid-stimulating hormone, β subunit E2-ERα, 17β-estradiol-bound estrogen receptor α T3, tri-iodothyronine |
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