Diagnostic methods to predict the development of autoimmune diseases by gene polymorphisms of immune regulatory factors

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390150
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Osaka University
• Principal Investigator: YOSHINORI Iwatani 大阪大学, 医学(系)研究科(研究院), 教授 (60168581)
• Co-Investigator(Kenkyū-buntansha): HIDAKA Yoh 大阪大学, 大学院・医学系研究科, 准教授 (30243231) ; WATANABE Mikio (50294088)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 免疫応答制御因子 / 遺伝子多型 / 自己免疫疾患 / 発症予知診断法 / 疾患感受性遺伝子 / サイトカイン / DNAメチル化酵素

Research Abstract

In order to develop the predictive diagnostic methods for the development and prognosis of autoimmune thyroid diseases, we analyzed the single mononucleotide polymorphisms (SNPs) of immune regulatory factors in patients with Hashimoto's disease and with Graves' disease. We clarified the usefulness of ZFAT Ex9b-SNP10T/A, MTRR +66A/G, IL-10 -592A/C and TSHR rs179247A/G SNPs to predict the development of hypothyroidism under 50 years old in patients with Hashimoto's disease, and that of TBX21 -1514T/C, HLX -742C/G, IL-13 -1112C/T, CD40 -1C/T,FCRL3 -169C/T, DNMT1 +32204A/G and TSHR rs179247A/G SNPs to predict the intractability of Graves' disease against anti-thyroid drug therapy. Furthermore, we clarified the importance of an EPO -1125G/T SNP which determine the strength of angiogenic capability for the development of Graves' disease. These data indicate that the SNPs of immune regulatory factors are useful for the predictive diagnostic methods for autoimmune diseases.

Research Products

• [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 Pages: 156-158
  • DOI: 10.1016/j.imlet.2013.10.006
• [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 Pages: 288-290
  • DOI: 10.1111/tan.12190
• [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 Pages: 370-374
  • DOI: 10.1016/j.cyto.2013.05.014
• [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 Pages: 245-252
  • DOI: 10.3109/00365513.2013.769624
• [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) Pages: 161-3
  • DOI: 10.1111/tan.12070
• [Journal Article] An overview of multidisciplinary research resorces at the Osaka University Center for Twin Research (2013)
  • Author(s): Hayakawa, K., Iwatani, Y
  • Journal Title: Twin Res Hum genet
  • DOI: 10.1017/thg.2012.141
• [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) Pages: 137-44
  • DOI: 10.1530/EJE-12-0507
• [Journal Article] Interference by Pralidoxime (PAM) salts in clinical laboratory tests (2013)
  • Author(s): Nagase, S., Kohguchi, K., Tohyama, K., Watanabe, M., Iwatani, Y
  • Journal Title: Clin Chim Acta Volume: 416 Pages: 72-79
  • DOI: 10.1016/j.cca.2012.11.017
• [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) Pages: 194-201
  • DOI: 10.1111/j.1365-2249.2012.04646.x
• [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 Pages: 1243-52
  • DOI: 10.1007/s10875-012-9721-0
• [Journal Article] Masurement of TFF3 mRNA in aspirates from thyroid nodules using mesh filtration : The first clinical trial in 130 cases (2012)
  • Author(s): Yamada, H., Takano, T., Kihara, M., Hirokawa, M., Yoshida, H., Watanabe, M., Iwatani, Y., Hidaka, Y., Miyauchi, A
  • Journal Title: Endocrine J Volume: 59(7) Pages: 621-30
  • DOI: 10.1507/endocrj.EJ12-0077
• [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 (2012)
  • Author(s): Yamada, H., Yamakawa, N., Watanabe, M., Hidaka, Y., Iwatani, Y., Takano, T
  • Journal Title: Biotech Histochem Volume: 87(5) Pages: 366-71
  • DOI: 10.3109/10520295.2012.672650
• [Journal Article] Functional polymorphisms in TBX21 and HLX are associated with development and prognosis of Graves' disease (2012)
  • 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: 10.3109/08916934.2011.622013
• [Journal Article] Preparation of a cut-off solution that gives a clear index for distinguishing Le(a-b-) sera in CA19-9 assays using SphereLight 180 and Architect i2000 kits (2012)
  • Author(s): Hanada, H., Mugii, S., Takeoka, K., Maeda, I., Watanabe, M., Hidaka, Y., Iwatani, Y
  • Journal Title: Clinica Chemica Acta Volume: 413(1-2) Pages: 278-281
• [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
• [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: Clin Exp Immunol Volume: 163(3) Pages: 318-323
• [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
• [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
• [Journal Article] Evaluation of amphotericin B and micafungin combination against clinical isolates of Aspergillus species (2011)
  • Author(s): Nishi, I., Sunada, A., Toyokawa, M., Asari, S., Iwatani, Y
  • Journal Title: J Chemother Volume: 23(2) Pages: 102-6
• [Remarks]
  • URL: http://sahswww.med.osaka-u.ac.jp/~prevdiag/