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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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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.
Toxicology Letters 03/2013; · 3.23 Impact Factor
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Ayako Kanazawa,
Chihiro Miyasita,
Emiko Okada, Sumitaka Kobayashi,
Noriaki Washino,
Seiko Sasaki,
Eiji Yoshioka,
Futoshi Mizutani,
Youichi Chisaki,
Yasuaki Saijo,
Reiko Kishi
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ABSTRACT: The aim of this study was to document the exposure levels of pregnant women in Hokkaido to persistent organochlorine (POC) pesticides and the relationship between the body burdens of these pesticides and the study population's characteristics, such as age, pre-pregnancy body weight and calendar year in which blood was collected. From 2002 to 2005, whole blood samples were obtained from 186 pregnant women (aged 17 to 47 years) from the population of 514 women registered with the Sapporo Toho hospital cohort of the Hokkaido Study. Blood samples were analyzed by GC/NCIMS and GC/HRMS to quantify 29 POC pesticides. The subjects' demographic details were obtained from medical records and self-administered questionnaires. The Jonckheere-Terpstra test was used to determine relevant trends in the chemical concentrations of these pesticides and their relationship to the subjects' demographic details. Twenty-one of the 29 targeted compounds (including pesticides that have never been used in Japan, such as Mirex, Parlar-26 and Parlar-50) were detected in whole blood samples, and their log-transformed concentrations were found to significantly correlate with each other. The concentrations of p,p'-DDD, o,p'-DDE, p,p'-DDE, Parlar-26 and Parlar-50 declined from 2002 to 2005 (p<0.05). The pesticide concentrations appeared to have stronger associations with past conception than with parity, with most pesticide concentrations declining in a manner that appeared inversely related to past conceptions (p<0.05). Maternal age was positively associated with the following pesticide concentrations: p,p'-DDE, chlordanes group, cis-heptachlorepoxide, β-HCH and mirex. Maternal pre-pregnancy body weight was positively associated with the concentrations of dieldrin, HCB, β-HCH, Parlar-26 and Parlar-50, and appeared to be more strongly related to the body burdens of POC pesticides when compared with BMI associations. Further studies are required to evaluate the effects of POC pesticides on human health with regard to reproductive outcomes and child development.
Science of The Total Environment 04/2012; 426:73-82. · 3.29 Impact Factor
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Thamar Ayo Yila,
Seiko Sasaki,
Chihiro Miyashita,
Titilola Serifat Braimoh,
Ikuko Kashino, Sumitaka Kobayashi,
Emiko Okada,
Toshiaki Baba,
Eiji Yoshioka,
Hisanori Minakami,
Toshiaki Endo,
Kazuo Sengoku,
Reiko Kishi
[show abstract]
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ABSTRACT: Intracellular folate hemostasis depends on the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. Because 5,10-MTHFR 677TT homozygosity and tobacco smoking are associated with low folate status, we tested the hypothesis that smoking in mothers with 5,10-MTHFR C677T or A1298C polymorphisms would be independently associated with lower birth weight among their offspring.
We assessed 1784 native Japanese mother-child pairs drawn from the ongoing birth cohort of The Hokkaido Study on Environment and Children's Health. Data (demographic information, hospital birth records, and biological specimens) were extracted from recruitments that took place during the period from February 2003 to March 2006. Maternal serum folate were assayed by chemiluminescent immunoassay, and genotyping of 5,10-MTHFR C677T/A1298C polymorphisms was done using a TaqMan allelic discrimination assay.
The prevalence of folate deficiency (<6.8 nmol/L) was 0.3%. The 5,10-MTHFR 677CT genotype was independently associated with an increase of 36.40 g (95% CI: 2.60 to 70.30, P = 0.035) in mean infant birth weight and an increase of 90.70 g (95% CI: 6.00 to 175.50, P = 0.036) among male infants of nonsmokers. Female infants of 677TT homozygous passive smokers were 99.00 g (95% CI: -190.26 to -7.56, P = 0.034) lighter. The birth weight of the offspring of smokers with 5,10-MTHFR 1298AA homozygosity was lower by 107.00 g (95% CI: -180.00 to -33.90, P = 0.004).
The results suggest that, in this population, maternal 5,10-MTHFR C677T polymorphism, but not the 5,10-MTHFR A1298C variant, is independently associated with improvement in infant birth weight, especially among nonsmokers. However, 5,10-MTHFR 1298AA might be associated with folate impairment and could interact with tobacco smoke to further decrease birth weight.
Journal of Epidemiology 03/2012; 22(2):91-102. · 1.86 Impact Factor
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Thamar Ayo Yila,
Seiko Sasaki,
Chihiro Miyashita,
Titilola Serifat Braimoh,
Ikuko Kashino, Sumitaka Kobayashi,
Emiko Okada,
Toshiaki Baba,
Eiji Yoshioka,
Hisanori Minakami,
Toshiaki Endo,
Kazuo Sengoku,
Reiko Kishi
[show abstract]
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ABSTRACT: Background: Intracellular folate hemostasis depends on the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. Because 5,10-MTHFR 677TT homozygosity and tobacco smoking are associated with low folate status, we tested the hypothesis that smoking in mothers with 5,10-MTHFR C677T or A1298C polymorphisms would be independently associated with lower birth weight among their offspring.
Methods: We assessed 1784 native Japanese mother-child pairs drawn from the ongoing birth cohort of The
Hokkaido Study on Environment and Children’s Health. Data (demographic information, hospital birth records, and biological specimens) were extracted from recruitments that took place during the period from February 2003 to March 2006. Maternal serum folate were assayed by chemiluminescent immunoassay, and genotyping of 5,10-MTHFR C677T/A1298C polymorphisms was done using a TaqMan allelic discrimination assay.
Results: The prevalence of folate deficiency (<6.8 nmol/L) was 0.3%. The 5,10-MTHFR 677CT genotype was
independently associated with an increase of 36.40 g (95% CI: 2.60 to 70.30, P = 0.035) in mean infant birth weight and an increase of 90.70 g (95% CI: 6.00 to 175.50, P = 0.036) among male infants of nonsmokers. Female infants of 677TT homozygous passive smokers were 99.00 g (95% CI: −190.26 to −7.56, P = 0.034) lighter. The birth weight of the offspring of smokers with 5,10-MTHFR 1298AA homozygosity was lower by 107.00 g (95% CI: −180.00 to −33.90, P = 0.004).
Conclusions: The results suggest that, in this population, maternal 5,10-MTHFR C677T polymorphism, but not the 5,10-MTHFR A1298C variant, is independently associated with improvement in infant birth weight, especially among nonsmokers. However, 5,10-MTHFR 1298AA might be associated with folate impairment and could interact with tobacco smoke to further decrease birth weight.
Journal of Epidemiology / Japan Epidemiological Association. 01/2012; 22(2):91-102.
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Emiko Okada,
Seiko Sasaki,
Yasuaki Saijo,
Noriaki Washino,
Chihiro Miyashita, Sumitaka Kobayashi,
Kanae Konishi,
Yoichi M Ito,
Rie Ito,
Ayako Nakata,
Yusuke Iwasaki,
Koichi Saito,
Hiroyuki Nakazawa,
Reiko Kishi
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ABSTRACT: Recent studies have shown effects of prenatal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) on infants in the general environmental levels. Laboratory animal studies have shown that exposure to PFOS and PFOA is associated with immunotoxic effects.
To investigate the relationship between maternal PFOS and PFOA levels and infant allergies and infectious diseases during the first 18 months of life. Cord blood immunoglobulin (Ig) E levels were also evaluated.
We conducted a prospective cohort study of pregnant women from 2002 to 2005 in Sapporo, Japan. Maternal PFOS and PFOA levels were measured in relation to cord blood IgE concentrations (n=231) and infant allergies and infectious diseases (n=343). Characteristics of mothers and their infants were obtained from self-administered questionnaires and medical records. Development of infant allergies and infectious diseases was determined from self-administered questionnaires at 18 months of age. Concentrations of PFOS and PFOA in maternal serum and concentrations of IgE in umbilical cord serum at birth were measured.
Cord blood IgE levels decreased significantly with high maternal PFOA concentration among female infants. However, there were no significant associations among maternal PFOS and PFOA levels and food allergy, eczema, wheezing, or otitis media in the 18 month-old infants (adjusted for confounders).
Although cord blood IgE level decreased significantly with high maternal PFOA levels among female infants, no relationship was found between maternal PFOS and PFOA levels and infant allergies and infectious diseases at age in 18 months.
Environmental Research 01/2012; 112:118-25. · 3.40 Impact Factor
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Thamar Ayo Yila,
Seiko Sasaki,
Chihiro Miyashita,
Titilola Serifat Braimoh,
Ikuko Kashino, Sumitaka Kobayashi,
Emiko Okada,
Toshiaki Baba,
Eiji Yoshioka,
Hisanori Minakami,
Toshiaki Endo,
Kazuo Sengoku,
Reiko Kishi
Journal of Epidemiology. 01/2012;
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ABSTRACT: Dioxin-like compounds are endocrine disruptors. The effects of prenatal exposure to environmental levels of dioxins on immune function during infancy have not been clarified, although dioxins induce immunosuppression in offspring of animals. Moreover, human studies have not assessed the effects of gender- or congener-specific differences. The purpose of this study was to investigate the association between dioxin levels in maternal blood and the risk of infection and allergies in infancy. We examined 364 mothers and their infants enrolled in a Hokkaido Study on Environment and Children's Health between 2002 and 2005 in Sapporo, Japan. Relevant information was collected from a baseline questionnaire during pregnancy, medical records at delivery, and a follow-up questionnaire when the child was 18 months of age that assessed development of allergies and infections in infancy. Dioxin-like compound levels in maternal blood were measured with high-resolution gas chromatography/high-resolution mass spectrometry. Relatively higher levels of polychlorinated dibenzofuran were associated with a significantly increased risk of otitis media, especially among male infants (odds ratio=2.5, 95% confidence interval=1.1-5.9). Relatively higher levels of 2,3,4,7,8-pentachlorodibenzofuran were also associated with a significantly increased risk of otitis media (odds ratio=5.3, 95% confidence interval=1.5-19). However, we observed a weak association between dioxin-like compound levels and allergic symptoms in infancy. At environmental levels, prenatal exposure to dioxin-like compounds may alter immune function and increase the risk of infections in infancy, especially among males. The compound 2,3,4,7,8-pentachlorodibenzofuran may be responsible for this.
Environmental Research 02/2011; 111(4):551-8. · 3.40 Impact Factor
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Ayako Kanazawa,
Chihiro Miyasita,
Emiko Okada, Sumitaka Kobayashi,
Noriaki Washino,
Motoyuki Yuasa,
Seiko Sasaki,
Eiji Yoshioka,
Futoshi Mizutani,
Youichi Chisaki,
Reiko Kishi
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ABSTRACT: Objectives: This study was performed to evaluate the levels of exposure to persistent organochlorine pesticides in pregnant women in Hokkaido. Methods: Whole-blood samples were obtained from 70 pregnant women aged 17 to 39 years in Hokkaido and analyzed to quantify 29 organochlorine pesticides by gas chromatography/negative ion chemical ionization mass spectrometry and gas chromatography/high-resolution mass spectrometry. Results: Among 29 target compounds, 20 were detected in the whole-blood samples. Mirex, Parlar-26, and Parlar-50, which have never been used in Japan, were identified in all samples, as well as 11 compounds that have been used in Japan. Log-transformed concentrations of compounds with detection rates above 60% linearly correlated with each other (p<0.01). p,p'-DDE exhibited the highest concentration, with a geometric mean of 730 pg/g wet weight. From the results of the Jonckheere-Terpstra trend test, body weight or age was positively associated with the concentrations of several compounds. Conclusions: We detected 22 organochlorine pesticides including pesticides with no history of use in Japan in the whole-blood samples from pregnant women in Hokkaido. Through long-distance transport mechanisms, these pollutants may distribute widely, and further surveillance of human blood, in addition to foods and the environment, should be conducted.
Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene) 01/2011; 66(1):95-107.