Contributing rate of environmental factors to clinical laboratory tests based on the data using twins

• Project/Area Number: 24590695
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Osaka University
• Principal Investigator: WATANABE MIKIO 大阪大学, 医学(系)研究科(研究院), 准教授 (50294088)
• Co-Investigator(Renkei-kenkyūsha): HAYAKAWA Kazuo 大阪大学, 医学系研究科, 教授 (70142594) ; KATO Kenji 神戸市立看護大学, 准教授 (70458404)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 臨床検査 / 双生児 / 環境因子 / エピゲノム / 遺伝因子 / メチル化

Outline of Final Research Achievements

This study was proposed to examine the environmental factors affecting to the clinical laboratory tests using monozygotic twins, who have completely concordant genetic background. We indicated preliminaly that the methylation rates were different among the genotypes of polymorphisms in gene encoding the methylation-related enzymes, and that they can affect to the prognosis of autoimmune thyroid diseases. In addition, we have found 25-30 discordant twin pairs in the positivity of thyroid-specific autoantibodies, and are analyzing the intra-pair differences of methylation rates using these twins.

Research Products

• [Journal Article] Association between functional polymorphisms in the Toll-like receptor 4 (TLR4) gene and HD severity. (2015)
  • Author(s): Inoue, N., Watanabe, M., Katsumata, Y., Ishido, N., Hidaka, Y., Iwatani, Y
  • Journal Title: Tissue Antigens Volume: 85 Issue: 3 Pages: 209-211
  • DOI: 10.1111/tan.12518
  • Peer Reviewed
• [Journal Article] The Relationship between Skewed X Chromosome Inactivation and the Prognosis of Graves’ and Hashimoto’s Diseases (2015)
  • Author(s): Ishido,N., Inoue, N., Watanabe, M., Hidaka, Y., Iwatani, Y
  • Journal Title: Thyroid Volume: 25 Issue: 2 Pages: 256-261
  • DOI: 10.1089/thy.2014.0318
  • Peer Reviewed
• [Journal Article] Expression Analysis of Stemness Genes in a Rat Thyroid Cell Line FRTL5. (2015)
  • Author(s): Shimasue, A., Yamakawa, N., Watanabe, M., Hidaka, Y., Iwatani, Y., Takano, T.
  • Journal Title: Exp Clin Endocrinol Diabetes Volume: 12348-54 Pages: 48-54
  • Peer Reviewed
• [Journal Article] The functional polymorphisms of VDR, GC and CYP2R1 are involved in the pathogenesis of autoimmune thyroid diseases. (2014)
  • Author(s): Inoue, N., Watanabe, M., Ishido, N., Katsumata, Y., Kagawa, T., Hidaka, Y., Iwatani, Y
  • Journal Title: Clin Exp Immunol Volume: 178 Issue: 2 Pages: 262-269
  • DOI: 10.1111/cei.12420
  • Peer Reviewed
• [Journal Article] Associations of single nucleotide polymorphisms in pri-miR-125a and the expression of mature miR-125a with the development and prognosis of autoimmune thyroid diseases. (2014)
  • Author(s): Inoue, Y., Watanabe, M., Inoue, N., Kagawa, T., Shibutani, S., Otsu, H., Saeki, M., Takuse, Y., Hidaka, Y., Iwatani, Y.
  • Journal Title: Clin Exp Immunol Volume: 178 Issue: 2 Pages: 229-235
  • DOI: 10.1111/cei.12410
  • Peer Reviewed
• [Journal Article] Genes that characterize T3-predominant Graves' thyroid tissues (2013)
  • Author(s): Matsumoto, C., Ito, M., Yamada, H., Yamakawa, N., Yoshida, H., Date, A., Watanabe, M., Hidaka, Y., Iwatani, Y., Miyauchi, A., Takano, T
  • Journal Title: Eur J Endocrinol Volume: 168(2) Issue: 2 Pages: 137-44
  • DOI: 10.1530/eje-12-0507
  • Peer Reviewed
• [Journal Article] The association between a functional polymorphism in the CD24 gene and the development of autoimmune thyroid diseases (2013)
  • Author(s): Inoue, N., Watanabe, M., Hayashi F., Hidaka, Y., Iwatani, Y
  • Journal Title: Tissue Antigen Volume: 81(3) Issue: 3 Pages: 161-3
  • DOI: 10.1111/tan.12070
  • Peer Reviewed
• [Journal Article] Preparation of thyroid follicular cells for mRNA quantifi cation after fl uorescence-activated cell sorting (2013)
  • Author(s): Matsumoto, C., Ito, M., Yamada, H., Yoshida, H., Watanabe, M., Hidaka, Y., Iwatani, Y., Miyauchi, A., Takano, T
  • Journal Title: Scandinavian Journal of Clinical & Laboratory Investigation Volume: 73 Issue: 3 Pages: 245-252
  • DOI: 10.3109/00365513.2013.769624
  • Peer Reviewed
• [Journal Article] IL-10 -592A/C polymorphism is associated with severity of Hashimoto's disease (2013)
  • Author(s): Inoue, N., Watanabe, M., Wada, M., Morita, M., Hidaka, Y., Iwatani, Y
  • Journal Title: Cytokine Volume: 64 Issue: 1 Pages: 370-374
  • DOI: 10.1016/j.cyto.2013.05.014
  • Peer Reviewed
• [Journal Article] Different genotypes of a functional polymorphism of the TSHR gene are associated with the development and severity of Graves and Hashimotos diseases (2013)
  • Author(s): Inoue, N., Watanabe, M., Katsumata, Y., Hidaka, Y., Iwatani, Y
  • Journal Title: Tissue Antigen Volume: 82 Issue: 4 Pages: 288-290
  • DOI: 10.1111/tan.12190
  • Peer Reviewed
• [Journal Article] The GG genotype of the 1125G/T polymorphism in the EPO gene protects against the development of Graves' disease (2013)
  • Author(s): Inoue, N. Watanabe, M., Nobuhara, T., Hidaka, Y., Iwatani, Y
  • Journal Title: Immunol Letters Volume: 156 Issue: 1-2 Pages: 156-158
  • DOI: 10.1016/j.imlet.2013.10.006
  • Peer Reviewed
• [Journal Article] The association between a functional polymorphism in the CD24 gene and the development of autoimmune thyroid diseases (2013)
  • Author(s): Inoue, N., Watanabe, M., Hayashi F., Hidaka, Y., Iwatani, Y.
  • Journal Title: Tissue Antigen Volume: in press
  • Peer Reviewed
• [Journal Article] Associations between autoimmune thyroid disease prognosis and functional polymorphisms of susceptibility genes, CTLA4, PTPN22, CD40, FCRL3, and ZFAT, previously revealed in Genome-wide association studies (2012)
  • Author(s): Inoue, N. Watanabe, M., Yamada, H., Takemura, K., Hayashi, F., Yamakawa, N., Akahane, M., Shimizuishi, Y., Hidaka, Y., Iwatani, Y
  • Journal Title: J Clin Immunol Volume: 32 Issue: 6 Pages: 1243-52
  • DOI: 10.1007/s10875-012-9721-0
  • Peer Reviewed
• [Journal Article] Association ofpolymorphisms in DNMT1, DNMT3A, DNMT3B, MTHFR, and MTRR genes with global DNA methylation levels and prognosis of autoimmune thyroid disease (2012)
  • Author(s): Arakawa, Y., Watanabe, M., Inoue, N., Sarumaru, M., Hidaka, Y., Iwatani, Y
  • Journal Title: Clin Exp Immunol Volume: 170(2) Issue: 2 Pages: 194-201
  • DOI: 10.1111/j.1365-2249.2012.04646.x
  • Peer Reviewed
• [Journal Article] Functional polymorphisms in TBX21 and HLX are associated with development and prognosis of Graves' disease (2011)
  • Author(s): Morita, M., Watanabe, M., Inoue, N., Inaoka, C., Akamizu, T., Tatsumi, K., Hidaka, Y., Iwatani, Y.
  • Journal Title: Autoimmunity Volume: 45(2) Issue: 2 Pages: 129-36
  • DOI: 10.3109/08916934.2011.622013
  • Peer Reviewed
• [Presentation] ヒトにおける自己免疫性甲状腺疾患の発症因子と病態規定因子（シンポジウム「自己免疫性甲状腺疾患の病因・病態はどこまで明らかになったか」） (2014)
  • Author(s): 渡邉幹夫
  • Organizer: 第57回日本甲状腺学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-11-13 – 2014-11-15
  • Invited
• [Presentation] バセドウ病と橋本病の感受性にそれぞれ異なる関連を示すTSHR遺伝子の機能的多型 (2014)
  • Author(s): 渡邉幹夫、井上直哉、勝又由佳、日高洋、岩谷良則
  • Organizer: 第42回日本臨床免疫学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-09-25 – 2014-09-26
• [Presentation] Different genotypes of a functional polymorphism of the THSR gene are associated with the development and severity of Graves' and Hashimoto's diseases. (2014)
  • Author(s): Watanabe, M., Inoue, N., Katsumata, Y., Hidaka, Y., Iwatani, Y.
  • Organizer: AACC Annual Meeting & Clinical Lab Expo 2014
  • Place of Presentation: Chicago
  • Year and Date: 2014-07-27 – 2014-07-31
• [Presentation] Functional polymorphisms in TBX21 and HLX are associated with development and prognosis of Graves' disease (2012)
  • Author(s): Watanabe, M., Morita, M., Inoue, N., Inaoka, C., Akamizu, T., Tatsumi, K., Hidaka, Y., Iwatani, Y.
  • Organizer: AACC Annual Meeting & Clinical Lab Expo 2012
  • Place of Presentation: Los Angeres（アメリカ）
• [Presentation] 自己免疫性甲状腺疾患の病態予後と全ゲノム関連解析による疾患関連遺伝子であるCTLA4, PTPN22, CD40, FCRL3, ZFAT遺伝子の機能的多型との関係 (2012)
  • Author(s): 渡邉幹夫、井上直哉、山田宏哉、武村和哉、林文明、山川法子、赤羽舞子、清水石裕、日高洋、岩谷良則
  • Organizer: 第19回日本遺伝子診療学会大会
  • Place of Presentation: 三井ガーデンホテル千葉（千葉）
• [Presentation] Associations between autoimmune thyroid disease prognosis and functional polymorphisms of susceptibility genes, CTLA4, PTPN22, CD40, FCRL3, and ZFAT, previously revealed in Genome-wide association studies
  • Author(s): M. WATANABE, N. Inoue, H. Yamada, K. Takemura, F. Hayashi, N. Yamakawa, M. Akahane, Y. Shimizuishi, Y. Hidaka, Y. Iwatani.
  • Organizer: The AACC annual meeting 2013
  • Place of Presentation: Houston（アメリカ）
• [Presentation] GITRの発現に影響する機能的遺伝子多型とバセドウ病および橋本病の予後との関連
  • Author(s): 渡邉幹夫、富澤理恵、井上直哉、武村和哉、日高洋、岩谷良則
  • Organizer: 第56回日本甲状腺学会
  • Place of Presentation: 和歌山市