Diagnostic methods to predict the development and the prognosis of autoimmune diseases based on the reguratory mechanisms for gene expression

• Project/Area Number: 26293128
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Osaka University
• Principal Investigator: Iwatani Yoshinori 大阪大学, 医学(系)研究科(研究院), 教授 (60168581)
• Co-Investigator(Kenkyū-buntansha): 日高 洋 大阪大学, 医学(系)研究科(研究院), 准教授 (30243231) ; 渡邉 幹夫 大阪大学, 医学(系)研究科(研究院), 准教授 (50294088)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000); Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: マイクロＲＮＡ / 遺伝子多型 / エピジェネティクス / 自己免疫疾患 / 予防医学 / マイクロRNA

Outline of Final Research Achievements

In order to develop the predictive diagnostic methods for the development and prognosis of autoimmune diseases, we examined noncoding RNA such as microRNA (miRNA, miR) and epigenetic changes such as DNA methylation and histone modification, both of which have important roles in the regulation of gene expression in autoimmune thyroid diseases. Then, we found that some miRs (miR-146a, miR-125a, and let-7a), enzymes necessary for miR production (Dicer and Drosha) and for histome modification (SIRT1), single nucleotide polymorphisms of genes (TLR, IL15, TSHR, VDR, FASL, BCL, IL8, RANTES, and MIG) and the expression of these genes were useful for predicting the development and/or prognosis of autoimmune thyroid diseases. These data indicates that these regulatory factors of gene expression and single nucleotide polymorphisms can be used to develop the predictive diagnostic methods for autoimmune diseases.

Research Products

• [Journal Article] TSHR gene polymorphisms in the enhancer regions are most strongly associated with the development of Graves’ disease, especially intractable disease, and with that of Hashimoto’s disease. (2017)
  • Author(s): Fujii, A., Inoue, N., Watanabe, M., Kawakami, C., Hidaka, Y., Hayashizaki, Y. and Iwatani, Y.
  • Journal Title: Thyroid Volume: 27 Issue: 1 Pages: 111-119
  • DOI: 10.1089/thy.2016.0345
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Intraindividual variation of microRNA expression levels in plasma and peripheral blood mononuclear cells and the associations of these levels with the pathogenesis of autoimmune thyroid diseases. (2017)
  • Author(s): Otsu, H., Watanabe, M., Inoue, N., Masutani, R., Iwatani, Y.
  • Journal Title: Clin Chem Lab Med Volume: 55 Issue: 5 Pages: 626-635
  • DOI: 10.1515/cclm-2016-0449
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The IL15 +96522 A>T functional polymorphism is related to the differentiation of Th17 cells and the severity of Hashimoto’s disease. (2017)
  • Author(s): Arakawa, Y. Watanabe, M., Takemura, K., Inoue, N., Hidaka, Y., Iwatani, Y.
  • Journal Title: International Journal of Immunogenetics Volume: 44 Issue: 2 Pages: 41-50
  • DOI: 10.1111/iji.12305
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Involvement of genes encoding apoptosis regulatory factors (FAS, FASL, TRAIL, BCL2, TNFR1 and TNFR2) in the pathogenesis of autoimmune thyroid diseases . (2016)
  • Author(s): Inoue, N., Watanabe, M., Ishido, N., Kodu, A., Maruoka, H., Katsumata, Y., Hidaka, Y., Iwatani, Y.
  • Journal Title: Hum Immunol Volume: 77 Issue: 10 Pages: 944-945
  • DOI: 10.1016/j.humimm.2016.07.232
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] DICER and DROSHA gene expression and polymorphisms in autoimmune thyroid diseases . (2016)
  • Author(s): Saeki, M., Watanabe, M., Inoue, N., Tokiyoshi, E. Takuse, Y., Arakawa, Y. Hidaka, Y., Iwatani, Y.
  • Journal Title: Autoimmunity Volume: 49 Pages: 514-522
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Within-pair differences of DNA methylation levels between monozygotic twins are different between male and female pairs. (2016)
  • Author(s): Watanabe, M., Honda, C., The Osaka Twin Research Group, Iwatani, Y.
  • Journal Title: BMC Medical Genomics Volume: 9 Issue: 1 Pages: 55-63
  • DOI: 10.1186/s12920-016-0217-2
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Optimization of recovery and analysis of RNA in sorted cells in mRNA quantification after fluorescence-activated cell sorting. (2016)
  • Author(s): Maeda, T., Date, A., Watanabe, M., Hidaka, Y., Iwatani, Y., Takano, T.
  • Journal Title: Ann Clin Lab Sci Volume: 46 Pages: 435-441
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Polymorphisms in and expression of Toll-like receptors in autoimmune thyroid diseases. (2016)
  • Author(s): Inoue, N., Katsumata, Y., Watanabe, M., Ishido, N., Manabe, Y., Watanabe, A., Masutani, R., Hidaka, Y., Iwatani, Y.
  • Journal Title: Autoimmunity Volume: 26 Issue: 3 Pages: 1-10
  • DOI: 10.1080/08916934.2016.1261835
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Increases of microRNA let-7e in peripheral blood mononuclear cells in Hashimoto's disease. (2016)
  • Author(s): Kagawa T, Watanabe M, Inoue N, Otsu H, Saeki M, Katsumata Y, Takuse Y, Iwatani Y.
  • Journal Title: Endocrine J Volume: 63
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association of polymorphisms in the <i>ICOS</i> and <i>ICOSL</i> genes with the pathogenesis of autoimmune thyroid diseases (2016)
  • Author(s): Yoshie N, Watanabe M, Inoue N, Kawaguchi H, Hidaka Y, Iwatani Y.
  • Journal Title: Endocrine Journal Volume: 63 Issue: 1 Pages: 61-68
  • DOI: 10.1507/endocrj.EJ15-0435
  • NAID: 130005121495
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association of the polymorphisms of chemokine genes (IL8, RANTES, MIG, IP10, MCP1 and IL16) with the pathogenesis of autoimmune thyroid diseases. (2016)
  • Author(s): Akahane M, Watanabe M, Inoue N, Miyahara U, Arakawa Y, Inoue Y, Katsumata Y, Hidaka Y, Iwatani Y.
  • Journal Title: Autoimmunity Volume: 49
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association between functional SIRT1 polymorphisms and the clinical characteristics of patients with autoimmune thyroid disease. (2016)
  • Author(s): Sarumaru M, Watanabe M, Inoue N, Hisamoto Y, Morita E, Arakawa Y, Hidaka Y, Iwatani Y.
  • Journal Title: Autoimmunity Volume: 49
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age: A Study of the CODATwins Project. (2015)
  • Author(s): Aline Jelenkovic, Yoshie Yokoyama, Reijo Sund, Chika Honda et al.
  • Journal Title: Twin Research and Human Genetics Volume: 18 Issue: 5 Pages: 557-570
  • DOI: 10.1017/thg.2015.57
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The CODATwins Project: The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits (2015)
  • Author(s): Karri Silventoinen, Aline Jelenkovic, Reijo Sund, et al.
  • Journal Title: Twin Research and Human Genetics Volume: 18(4) Issue: 4 Pages: 348-360
  • DOI: 10.1017/thg.2015.29
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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] 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] In vitro evaluations of topical agents to treat Acanthamoeba keratitis. (2014)
  • Author(s): Sunada A, Kimura K, Nishi I, Toyokawa M, Ueda A, Sakata T, Suzuki T, Inoue Y, Ohashi Y, Asari S,Iwatani Y.
  • Journal Title: Ophthalmology Volume: 121 Issue: 10 Pages: 2059-2065
  • DOI: 10.1016/j.ophtha.2014.04.013
  • Peer Reviewed
• [Remarks] 大阪大学大学院医学系研究科保健学専攻生体情報科学講座 予防診断学研究室
  • URL: http://sahswww.med.osaka-u.ac.jp/~prevdiag/
• [Remarks] 大阪大学大学院医学系研究科保健学専攻生体情報科学講座 予防診断学研究室
  • URL: http://sahswww.med.osaka-u.ac.jp/~prevdiag/