Effect of maternal folate status in early pregnancy on childhood asthma through epigenetic modulation

• Project/Area Number: 25860433
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Epidemiology and preventive medicine
• Research Institution: Hokkaido University
• Principal Investigator: MIYASHITA Chihiro 北海道大学, 環境健康科学研究教育センター, 特任准教授 (70632389)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 環境疫学 / 分子遺伝疫学 / 妊婦 / 葉酸 / 小児喘息 / 発症リスク / アレルギー / DNAメチル化 / 遺伝子変異 / SNPs / SNPｓ

Outline of Final Research Achievements

Subjects of 1262 mother-child pairs who have been recruited on the Hokkaido birth cohort study, were included in this study. The median concentration of folic acid during first trimester in maternal serum was 7.3 ng/ml, and there was no significant difference between a case group of developing asthma and a control group of non-asthma at 7 years old children. There were no associations between concentration of serum folate (continuous), or folic acid supplement intake (categorical) and risk of asthma at 7 years old children. In this study, we could not observe the adverse effect of folic acid state during pregnancy on risk of asthma at 7 years old children. In a future study, we will stratify subjects into 3 groups of deficient, insufficient, or sufficient serum folate levels and analyze genetic factor using children saliva and DNA samples with a larger sample size.

Research Products

• [Journal Article] Effects of in utero exposure to polychlorinated biphenyls, methylmercury, and polyunsaturated fatty acids on birth size (2015)
  • Author(s): C. Miyashita, S. Sasaki, T. Ikeno, A. Araki, S. Ito, J. Kajiwara, T. Todaka, N. Hachiya, A. Yasutake, K. Murata, T. Nakajima and R. Kishi
  • Journal Title: Sci Total Environ Volume: 533 Pages: 256-265
  • DOI: 10.1016/j.scitotenv.2015.06.108
  • Peer Reviewed / Open Access
• [Journal Article] Demographic, behavioral, dietary and socioeconomic characteristics related to persistent organic pollutants and mercury levels in pregnant woman in Japan (2015)
  • Author(s): Miyashita C., Sasaki S., Saijo Y., Okada E., Kobayashi S., Baba T., Kajiwara J., Todaka T., Iwasaki Y., Nakazawa H., Hachiya N., Yasutake A., Murata K., Kishi R.
  • Journal Title: Chemosphere Volume: 133 Pages: 13-21
  • DOI: 10.1016/j.chemosphere.2015.02.062
  • Peer Reviewed / Open Access
• [Journal Article] Associations of Perfluoroalkyl Substances (PFASs) with Lower Birth Weight: An Evaluation of Potential Confounding by Glomerular Filtration Rate Using a Physiologically Based Pharmacokinetic Model (PBPK). (2015)
  • Author(s): M. A. Verner, A. E. Loccisano, N. H. Morken, M. Yoon, H. Wu, R. McDougall, M. Maisonet, M. Marcus, R. Kishi, C. Miyashita, M. H. Chen, W. S. Hsieh, M. E. Andersen, H. J. Clewell, 3rd and M. P. Longnecker.
  • Journal Title: Environ Health Perspect Volume: 123 Issue: 12 Pages: 1317-1317
  • DOI: 10.1289/ehp.1408837
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The Association of Prenatal Exposure to Perfluorinated Chemicals with Maternal Fatty Acids during Pregnancy and the Birth Weight of their Offspring:The Hokkaido Study (2015)
  • Author(s): Reiko Kishi, Tamie Nakajima, Houman Goudarzi, Sachiko Kobayashi, Seiko Sasaki, Emiko Okada, Chihiro Miyashita, Sachiko Itoh, Atsuko Araki, Tamiko Ikeno, Yusuke Iwasaki, and Hiroyuki Nakazawa
  • Journal Title: Environmental Health Perspective Volume: 印刷中 Issue: 10 Pages: 1038-1045
  • DOI: 10.1289/ehp.1408834
  • Peer Reviewed / Open Access
• [Journal Article] Prenatal exposure to perfluoroalkyl acids and allergic diseases in earlychildhood. (2014)
  • Author(s): Okada E, Sasaki S, Kashino I, Matsuura H, Miyashita C, Kobayashi S, Itoh K, Ikeno T, Tamakoshi A, Kishi R.
  • Journal Title: Environment International Volume: 65 Pages: 127-134
  • DOI: 10.1016/j.envint.2014.01.007
  • Peer Reviewed / Open Access
• [Journal Article] Temporal trends of perfiuoroalkyl acids in plasma samples of pregnant women in Hokkaido, Japan, 2003-2011. (2014)
  • Author(s): Okada E, Kashino I, Matsuura H, Sasaki S, Miyashita C, Yamamoto J, Ikeno T, Ito Y, Matsumura T, Yamakoshi A, Kishi R.
  • Journal Title: Environment International Volume: 60 Pages: 89-96
  • DOI: 10.1016/j.envint.2013.07.013
  • Peer Reviewed
• [Journal Article] 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 (2013)
  • Author(s): Kobayashi S, Sata F, Sasaki S, Ban S, Miyashita C, Okada E, Limpar M, Yoshioka E, Kajiwara J, Todaka T, Saijo Y, Kishi R
  • Journal Title: Toxicology Letters Volume: 219(3) Issue: 3 Pages: 269-278
  • DOI: 10.1016/j.toxlet.2013.03.013
  • NAID: 120005295676
  • Peer Reviewed
• [Journal Article] Ten years of progress in the Hokkaido birth cohort study on environment and children's health : cohort profile--updated 2013. (2013)
  • Author(s): Kishi R, Kobayashi S, Ikeno T, Araki A, Miyashita C, Itoh S, Sasaki S, Okada E, Kobayashi S, Kashino I, Itoh K, Nakajima S ; Members of the Hokkaido Study on Environment and Children's Health.
  • Journal Title: Environmental Health and Preventive Medicine Volume: 18 Issue: 6 Pages: 429-450
  • DOI: 10.1007/s12199-013-0357-3
  • Peer Reviewed
• [Journal Article] 妊婦のダイオキシン類代謝酵素遺伝子多型と母体血中ダイオキシン類濃度との関連 (2013)
  • Author(s): 小林澄貴, 佐田文宏, 佐々木成子, 坂晋, 宮下ちひろ, 岡田恵美子, Limpar Mariko, 吉岡英治, 梶原淳睦, 戸高尊, 西條泰明, 岸玲子
  • Journal Title: 北海道医学雑誌 Volume: 88 Pages: 145-145
  • NAID: 10031196495
• [Journal Article] 北海道における妊婦の血中有機フッ素化合物濃度の経年変化 (2013)
  • Author(s): 岡田恵美子, 樫野いく子, 松浦英幸, 佐々木成子, 宮下ちひろ, 山本潤, 池野多美子, 伊藤陽一, 松村徹, 玉腰暁子, 岸玲子
  • Journal Title: 北海道医学雑誌 Volume: 88 Pages: 203-203
• [Presentation] 胎児期ダイオキシン類曝露による臍帯血中性ホルモンへの影響：環境と子供の健康北海道スタディ. (2015)
  • Author(s): 宮下ちひろ，荒木敦子，三井貴彦，伊藤佐知子，佐々木成子，戸髙尊，梶原淳睦，長和俊，野々村克也，岸玲子.
  • Organizer: 第67回北海道公衆衛生学会
  • Place of Presentation: 旭川医科大学 (北海道・旭川市)
  • Year and Date: 2015-10-17
• [Presentation] Prenatal BPA exposure and cord blood adipokines, birth weight and child growth: the Hokkaido Study of Environment and Children’s health (2015)
  • Author(s): M. Minatoya, S. Sasaki, A. Araki, C. Miyashita, J. Yamamoto, T. Matsumura and R. Kishi
  • Organizer: The International Society for Environmental Epidemiology (ISEE)
  • Place of Presentation: San Paulo (Brazil)
  • Year and Date: 2015-08-30
  • Int'l Joint Research
• [Presentation] Effects of maternal AHR, CYP1A1 and GSTM1 polymorphisms and dioxins on infant birth weight: The Hokkaido Study (2015)
  • Author(s): S. Kobayashi, C. Miyashita, S. Sasaki, A. Araki, F. Sata, S. Ban, J. Kajiwara, T. Todaka and R. Kishi.
  • Organizer: The International Society for Environmental Epidemiology (ISEE)
  • Place of Presentation: San Paulo (Brazil)
  • Year and Date: 2015-08-30
  • Int'l Joint Research
• [Presentation] 臍帯血ビスフェノールA濃度と児のIGF2 DNAメチル化との関連-北海道スタディ (2015)
  • Author(s): 小林祥子，安住薫，佐々木成子，松村徹，山本潤，石塚真由美，宮下ちひろ，池野多美子，荒木敦子，岸玲子
  • Organizer: 第85回日本衛生学会学術総会.
  • Place of Presentation: 和歌山県民文化会館（和歌山県・和歌山市）
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] ダイオキシン類曝露と胎児発育との関連: 遺伝的なリスクについて―北海道スタディ―. (2015)
  • Author(s): 小林澄貴，宮下ちひろ，佐々木成子，荒木敦子，佐田文宏，坂晋，梶原淳睦，戸高尊，岸玲子
  • Organizer: 第85回日本衛生学会学術総会
  • Place of Presentation: 和歌山県民文化会館（和歌山県・和歌山市）
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] 有機塩素系農薬が乳幼児の免疫に与える影響―環境と子どもの健康北海道スタディー (2015)
  • Author(s): 宮下ちひろ，金澤文子，佐々木成子，池野多美子，荒木敦子，伊藤佐智子，小林祥子，水谷太，苣木洋一，岸玲子
  • Organizer: 第85回日本衛生学会学術総会
  • Place of Presentation: 和歌山県民文化会館（和歌山県・和歌山市）
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] 胎児期の有機塩素系農薬が小児アレルギー発症に与える影響―環境と子どもの健康北海道スタディー (2014)
  • Author(s): 宮下ちひろ，金澤文子，池野多美子，荒木敦子，伊藤佐智子，小林澄貴，湊屋街子，Houman Goudarzi，小林祥子，田村菜穂美，水谷太，苣木洋一，岸玲子
  • Organizer: 第66回北海道公衆衛生学会
  • Place of Presentation: 北海道大学学術交流会館 （北海道・札幌市）
  • Year and Date: 2014-12-02
• [Presentation] The effects of perfluoroalkyl acids (PFAAs) exposure in utero on IGF2/H19 DNA methylation in cord blood. (2014)
  • Author(s): Kobayashi S., Azumi K., Sasaki S., Ishizuka M., Nakazawa H., Okada E., Kobayashi S., Goudarzi H., Itoh S., Miyashita C., Ikeno T., Araki A., Kishi R.
  • Organizer: 26th Annual International Society for Environmental Epidemiology Conference
  • Place of Presentation: University of Washington, Seattle, USA
  • Year and Date: 2014-08-24 – 2014-08-28
• [Presentation] The Association Between Prenatal Exposure to Perfluoroalkyl Substances (PFAS) and Reduced Birth Weight: Is Glomerular Filtration Rate the Underlying Cause? (2014)
  • Author(s): Verner MA., Loccisano AE., Yoon M., Wu H., McDougall R., Maisonet M., Marcus M., Kishi R., Miyashita C., Chen MH., Hsieh W., Andersen M., Clewell III H., Longnecker MP.
  • Organizer: SOT's 53rd Annual Meeting
  • Place of Presentation: Phoenix Convention Center （USA）
• [Presentation] Maternal exposure to dehp and sex hormone levels in cord blood (2013)
  • Author(s): Araki A., Mitsui T., Miyashita C., Tagawa M., Nakajima T., Sasaki S., Ikeno T., Itoh S., Okada E., Cho K., Nonomura K., Kishi R.
  • Organizer: DOHaD2013-8th World Congress on DOHaD
  • Place of Presentation: サンテック・シンガポール国際会議展示場（シンガポール）
• [Presentation] The effects of hydroxylated PCBs in maternal serum on infant thyroid hormones (2013)
  • Author(s): Itoh S., Kajiwara J., Miyashita C., Kobayashi S., Sasaki S., Ban S., Ikeno T., Araki A., Kishi R.
  • Organizer: Environment and Health - Bridging South, North, East and West Conference of ISEE, ISES and ISIAQ
  • Place of Presentation: Congress Center Basel （スイス）
• [Presentation] Prenatal Exposure to 11 Perfluorinated Compounds (PFCs) and infant weight in the Hokkaido Study on Environmental and Children's Health (2013)
  • Author(s): Kashino I., Okada E., Sasaki S., Miyashita C., Ikeno T., Araki A., Yamamoto J., Matsuura H., Matsumura T., Tamakoshi A., Kishi R.
  • Organizer: Environment and Health - Bridging South, North, East and West Conference of ISEE, ISES and ISIAQ
  • Place of Presentation: Congress Center Basel （スイス）
• [Presentation] Relationship between prenatal exposure to perfluorinated compounds and allergic diseases in infants (2013)
  • Author(s): Okada E., Kashino I., Sasaki S., Miyashita C., Ikeno T., Araki A., Yamamoto J., Matsuura H., Matsumura T., Tamakoshi A., Kishi R.
  • Organizer: Environment and Health - Bridging South, North, East and West Conference of ISEE, ISES and ISIAQ
  • Place of Presentation: Congress Center Basel （スイス）
• [Remarks] 環境研究科学研究教育センター 研究業績
  • URL: http://www.cehs.hokudai.ac.jp/research/yearly/
• [Remarks] 環境健康科学研究教育センター 研究業績
  • URL: http://www.cehs.hokudai.ac.jp/research/yearly/
• [Remarks] 環境と健康ひろば
  • URL: http://www.cehs.hokudai.ac.jp/hiroba/
• [Remarks] 環境健康科学研究教育センター 研究業績
  • URL: http://www.cehs.hokudai.ac.jp/research/yearly/
• [Remarks] 環境と健康ひろば
  • URL: http://www.cehs.hokudai.ac.jp/hiroba/