Development of epigenetic factors for the prognosis of autoimmune thyroid disease using monozygotic twins

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590625
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Osaka University
• Principal Investigator: WATANABE Mikio 大阪大学, 大学院・医学系研究科, 助教 (50294088)
• Co-Investigator(Renkei-kenkyūsha): HAYAKAWA Kazuo 大阪大学, 大学院・医学系研究科, 教授 (70142594)
• Project Period (FY): 2009 – 2011
• Keywords: 病態予後 / 自己免疫疾患 / 遺伝子多型 / エピジェネティクス / メチル化

Research Abstract

We have collected genomic DNA samples from patients with autoimmune thyroid diseases who were strictly classified into categories depend on their prognosis, and also from monozygotic twin pairs. We have clarified the associations of some functional polymorphisms in immune regulatory genes with the prognosis of Graves' and Hashimoto' s diseases. In addition, we have reported for the first time that the global methylation of genomic DNA was related to the genotype of polymorphism in DNMT1 gene, which also associated with the prognosis of autoimmune thyroid diseases.

Research Products

• [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) Pages: 129-36
  • DOI: doi:10.3109/08916934.2011.622013
  • Peer Reviewed
• [Journal Article] Association of functional GITR gene polymorphisms related to expression of GITR molecules with prognosis of autoimmune thyroid disease (2011)
  • Author(s): Tomizawa, R., Watanabe, M., Inoue N., Takemura, K., Hidaka, Y., Akamizu, T., Hayakawa, K., Iwatani, Y.
  • Journal Title: Clin Exp Immunol Volume: 165(2) Pages: 141-147
  • DOI: doi:10.1111/j.1365-2249.2011.04414.x
  • Peer Reviewed
• [Journal Article] Association of functional polymorphisms in promoter regions of IL5, IL6, and IL13 genes with development and prognosis of autoimmune thyroid diseases (2011)
  • Author(s): Inoue, N., Watanabe, M., Morita, M., Tatsumi, K., Hidaka, Y., Akamizu, T., Iwatani, Y.
  • Journal Title: ClinExp Immunol Volume: 163(3) Pages: 318-23
  • DOI: doi:10.1111/j.1365-2249.2010.04306.x
  • Peer Reviewed
• [Journal Article] mRNA quantification after fluorescence activated cell sorting using locked nucleic acid probes (2011)
  • Author(s): Maruo, R., Yamada, H., Watanabe, M., Hidaka, Y., Iwatani, Y. Takano, T.
  • Journal Title: Mol Biotechnol Volume: 49(1) Pages: 42-47
  • DOI: doi:10.1007/s12033-011-9375-9
  • Peer Reviewed
• [Journal Article] Transcriptional activity of the 5'-flanking region of the thyroid transcription factor-1 gene in human thyroid cell lines (2011)
  • Author(s): Yamada, H., Takano, T., Matsuzuka, F., Watanabe, M., Miyauchi, A., Iwatani, Y.
  • Journal Title: Genet Mol Biol Volume: 34(1) Pages: 6-10
  • DOI: doi:10.1590/S1415-47572010005000109
  • Peer Reviewed
• [Journal Article] Association of functional polymorphisms related to the transcriptional level of FOXP3 with prognosis of autoimmune thyroid diseases (2010)
  • Author(s): Inoue, N., Watanabe, M., Morita, M., Tomizawa, R., Akamizu, T., Tatsumi, K., Hidaka, Y., Iwatani, Y.
  • Journal Title: ClinExpImmunol Volume: 162(3) Pages: 402-406
  • DOI: doi:10.1111/j.1365-2249.2010.04229.x
  • Peer Reviewed
• [Journal Article] Messenger RNA quantification after fluorescence activated cell sorting using in situ hybridization (2010)
  • Author(s): Yamada, H., Maruo, R., Watanabe, M., Hidaka, Y., Iwatani, Y., Takano, T.
  • Journal Title: Cytometry Part A Volume: 77(11) Pages: 1032-1037
  • DOI: doi:10.1002/cyto.a.20973
  • Peer Reviewed
• [Journal Article] Messenger RNA quantification after fluorescence activated cell sorting using intracellular antigens (2010)
  • Author(s): Yamada, H., Maruo, R., Watanabe, M., Hidaka, Y., Iwatani, Y., Takano, T.
  • Journal Title: Biochem BiophysResCommun Volume: 397(3) Pages: 425-428
  • DOI: doi:10.1016/j.bbrc.2010.05.112
  • Peer Reviewed
• [Journal Article] Increases in urinary creatinine and blood pressure during early pregnancy in preeclampsia (2010)
  • Author(s): Kuromoto, K., Watanabe, M., Adachi, K., Ohashi, K., Iwatani, Y.
  • Journal Title: Ann Clin Biochem Volume: 47(Pt 4) Pages: 336-342
  • DOI: doi:10.1258/acb.2010.090290
  • Peer Reviewed
• [Journal Article] Postpartum increase of serum thioredoxin concentrations and the relation to CD8 lymphocytes (2010)
  • Author(s): Kuroda, S., Watanabe, M., Santo, T., Shimizuishi, Y., Takano, T., Hidaka, Y., Kimura, T., Iwatani, Y.
  • Journal Title: Ann Clin Biochem Volume: 47(Pt 1) Pages: 62-66
  • DOI: doi:10.1258/acb.2009.009120
  • Peer Reviewed
• [Journal Article] Association of-31C/ T functional polymorphism in the interleukin-1beta gene with the intractability of Graves' disease and the proportion of Th17 cells (2009)
  • Author(s): Hayashi, F., Watanabe, M., Nanba, T., Inoue, N., Akamizu, T., Iwatani, Y.
  • Journal Title: Clin Exp Immunol Volume: 158(3) Pages: 281-286
  • DOI: doi:10.1111/j.1365-2249.2009.04034.x
  • Peer Reviewed
• [Journal Article] Increases of the Th1/ Th2 cell ratio in severe Hashimoto' s disease and in the proportion of Th17 cells in intractable Graves' disease (2009)
  • Author(s): Nanba, T., Watanabe, M., Inoue, N., Iwatani, Y.
  • Journal Title: Thyroid Volume: 19(5) Pages: 495-501
  • DOI: doi:10.1089/thy.2008.0423
  • Peer Reviewed
• [Journal Article] Involvement of functional polymorphisms in the TNFAgene in the pathogenesis of autoimmune thyroid diseases and production of anti-TSH receptor antibody (2009)
  • Author(s): Inoue, N., Watanabe, M., Nanba, T., Wada, M., Akamizu, T., Iwatani, Y.
  • Journal Title: Clin Exp Immunol Volume: 156(2) Pages: 199-204
  • DOI: DOI:10.1111/j.1365-2249.2009.03884.x
  • Peer Reviewed
• [Journal Article] Expression of nestin mRNA is a differentiation marker in thyroid tumors (2009)
  • Author(s): Yamada H., Takano, T., Ito, Y., Matsuzuka, F., Miya, A., Kobayashi, K., Yoshida, H., Watanabe, M., Iwatani, Y., Miyauchi, A.
  • Journal Title: Cancer Lett Volume: 280(1) Pages: 61-64
  • DOI: doi:10.1016/j.canlet.2009.02.006
  • Peer Reviewed
• [Journal Article] Prolonged hybridization with a cRNA probe improves the signal to noise ratio for in-tube in situ hybridization for quantification of mRNA after fluorescence-activated cell sorting
  • Author(s): Yamada, H., Yamakawa, N., Watanabe, M., Hidaka, Y., Iwatani, Y., Takano, T.
  • Journal Title: Biotech Histochem Volume: (in press)
  • DOI: doi:10.3109/10520295.2012.672650
  • Peer Reviewed
• [Presentation] DNMT1, 3a, 3b遺伝子の多型と自己免疫性甲状腺疾患の病態およびゲノムのメチル化率との関連 (2011)
  • Author(s): 荒川裕也、渡邉幹夫、井上直哉、日高洋、巽圭太、岩谷良則
  • Organizer: 第54回日本甲状腺学会学術集会(大阪)
  • Place of Presentation: 大阪
  • Year and Date: 2011-11-23
• [Presentation] Association of functional polymorphisms related to the transcriptional level of FOXP3 gene with prognosis of autoimmune thyroid diseases (2010)
  • Author(s): Watanabe, M., Inoue, N., Morita, M., Tomizawa, R., Akamizu, T., Tatsumi, K., Hidaka, Y., Iwatani, Y.
  • Organizer: 14th International Thyroid Congress(ITC)
  • Place of Presentation: Paris
  • Year and Date: 2010-09-13
• [Presentation] Measuring TFF3/ LGALS3 mRNA ratio in FNABS from thyroid nodule : a clinical trial of eighty cases (2010)
  • Author(s): Yamada, H., Takano, T., Kihara, M., Hirokawa, M., Yoshida, H., Watanabe, M., Hidaka, Y., Iwatani, Y., Miyauchi, A.
  • Organizer: 14th International Thyroid Congress(ITC)
  • Place of Presentation: Paris
  • Year and Date: 2010-09-13
• [Presentation] Preoperative diagnosis of thyroid nodules by measuresing TFF3/ LGALS3 mRNA(T/ G) ratio : A clinical trial of fifty cases (2010)
  • Author(s): Yamada, H., Takano, T., Kihara, M., Hirokawa, M., Yoshida, H., Watanabe, M., Iwatani, Y., Hidaka, Y., Miyauchi, A.
  • Organizer: 14th International Congress of Endocrinology(ICE)
  • Place of Presentation: Kyoto
  • Year and Date: 2010-03-29
• [Presentation] Increases of the Th1/ Th2 cell ratio in severe Hashimoto' s disease and in the proportion of Th17 cells in intractable Graves' disease (2010)
  • Author(s): Watanabe, M., Nanba, T., Inoue, N., Iwatani, Y.
  • Organizer: 14th International Congress of Endocrinology(ICE)
  • Place of Presentation: Kyoto
  • Year and Date: 2010-03-28
• [Presentation] Involvement of the functional polymorphisms in TNFA gene in the pathogenesis of autoimmune thyroid diseases and the production of anti-TSH receptor antibody (2009)
  • Author(s): Inoue, N., Watanabe, M., Nanba, T., Akamizu, T., Iwatani, Y.
  • Organizer: 9th Congress of the Asia and Oceania Thyroid Association(AOTA)
  • Place of Presentation: Nagoya
  • Year and Date: 2009-11-03
• [Presentation] Expression of nestin mRNA is a differentiation marker in thyroid tumors (2009)
  • Author(s): Yamada, H., Takano, T., Ito, Y., Matsuzuka, F., Miya, A., Kobayashi, K., Yoshida, H., Watanabe, M., Iwatani, Y., Miyauchi, A.
  • Organizer: 9th Congress of the Asia and Oceania Thyroid Association(AOTA)
  • Place of Presentation: Nagoya
  • Year and Date: 2009-11-03
• [Presentation] An in-tube in situ hybridization method for the novel stem cell detection system, FACS-mQ (2009)
  • Author(s): Maruo, R., Yamada, H., Takano T., Watanabe, M., Iwatani, Y., Hidaka, Y.
  • Organizer: 9th Congress of the Asia and Oceania Thyroid Association(AOTA)
  • Place of Presentation: Nagoya
  • Year and Date: 2009-11-03
• [Presentation] Association of the-31C/ T functional polymorphism in the interleukin-1βgene with the intractability of Graves' disease and the proportion of Th17 cells (2009)
  • Author(s): Watanabe, M., Hayashi, F., Nanba, T., Inoue, N., Akamizu, T., Iwatani, Y.
  • Organizer: 80th Annual Meeting of the American Thyroid Association
  • Place of Presentation: Palm Beach
  • Year and Date: 2009-09-25
• [Remarks]
  • URL: http://sahswww.med.osaka-u.ac.jp/~prevdiag/
• [Remarks]
  • URL: http://www.dma.jim.osaka-u.ac.jp/view?l=ja & u=6453