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Association of the CTLA-4 gene polymorphisms with type 1 diabetes and autoimmune thyroid diseases

Research Project

Project/Area Number 11671134
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionSaitama Medical School

Principal Investigator

AWATA Takuya  The Fourth Department of Internal Medicine, Saitama Medical School, Assistant Professor, 医学部, 助教授 (40184303)

Co-Investigator(Kenkyū-buntansha) INOUE Ikuo  The Fourth Department of Internal Medicine, Saitama Medical School, Instructor, 医学部, 講師 (60232526)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsType 1 diabetes / IDDM / Autoimmune thyroid diseases / Graves' disease / Hashimoto's thyroiditis / CTLA-4 / Polymorphism / Association
Research Abstract

We continued to analyze the genetics of type 1 diabetes in Japanese, and obtained the following results.
1. We already reported that G allele of the G49A polymorphism of the CTLA-4 gene was significantly increased in Japanese typical type 1 diabetes. In the present study, we found that G allele was significantly increased in patients who presented with diabetic ketoacidosis and patients who were positive for anti-IA-2 Ab.
2. Furthermore, as compared with type 1 diabetes patients or type 1 diabetes patients with anti-GAD Ab (+), G allele was significantly decreased in diabetic patients presenting the clinical characteristics of type 2 diabetes but anti-GAD Ab (+), suggesting that the CTLA-4 gene may modulate the onset and course of type 1 diabetes.
3. Although there was a report that the polymorphism of BETA2/NEUROD1, one of the transcription factors in pancreatic beta cells, was associated with type 1 diabetes, we could not confirm the association.
4. We found that amino acid variations of WFS1, which is the responsible gene for Wolfram syndrome (IDDM, DI, optic atrophy, deafness), were associated with type 1 diabetes in Japanese, suggesting that the WFS1 gene may have a role in the development of common type 1 diabetes as a nonautoimmune genetic basis.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Mori H et al.: "Association of the Pro12Ala substitution in peroxisome proliferator-activated receptor γ2 both with resistance to development of diabetes and with impairment of insulin secretion and disease severity in individuals with type 2 diabetes mellitus."Diabetes, . (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Abe T et al.: "CTLA4 gene polymorphism contributes to the mode of onset of diabetes with GAD antibody in Japanese patients : genetic analysis of diabetic patients with GAD antibody."Diabetic Med,. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Chiba M et al.: "Tyrosine hydroxylase gene microsatellite polymorphism associated with insulin resistance in depressive disorder."Metabolism. 49. 1145-1149 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Awata T et al.: "Missense variations of the gene responsible for Wolfram syndrome (WFS1/wolframin) in Japanese : possible contribution of the Arg456His mutation to type 1 diabetes as a nonautoimmune genetic basis."Biochem Biophys Res Commun. 268. 612-616 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Awata T et al.: "Lack of association of the Ala45Thr variant in the BETA2/NEUROD1 with type 1 diabetes in Japanese."Diabetes Res Clin Pract. 49. 61-63 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Abe T et al.: "CTLA4 gene polymorphism correlates with the mode of onset and presence of ICA512 in Japanese Type 1 diabetes."Diabetes Res Clin Pract. 46. 169-175 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Abe, T., Takino, H., Yamasaki, H., Ozaki, M., Sera, Y., Kondo, H., Sakamaki, H., Kawasaki, E., Awata, T., Yamaguchi, Y.and Eguchi, K.: "CTLA4 gene polymorphism correlates with the mode of onset and presence of ICA512 in Japanese Type 1 diabetes."Diabetes Res Clin Pract. 46. 169-175 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Awata, T., Inoue, K., Kurihara, S., Ohkubo, T., Inoue, I., Abe, T., Takino, H., Kanazawa, Y.and Katayama, S.: "Missense variations of the gene responsible for Wolfram syndrome ( WFS1/wolframin) in Japanese : possible contribution of the Arg456His mutation to type 1 diabetes as a nonautoimmune genetic basis."Biochem Biophys Res Commun. 268. 612-616 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Awata, T., Inoue, K., Inoue, I., Abe, T., Takino, H., Kanazawa, Y.and Katayama, S.: "Lack of association of the Ala45Thr variant in the BETA2/NEUROD1 with type 1 diabetes in Japanese."Diabetes Res Clin Pract. 49. 61-63 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Chiba, M., Suzuki, S., Hinokio, Y., Hirai, M., Satoh, Y., Tashiro, A., Utsumi, A., Awata, T., Hongo, M.and Toyota, T.: "Tyrosine hydroxylase gene microsatellite polymorphism associated with insulin resistance in depressive disorder."Metabolism. 49. 1145-1149 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mori, H., Ikegami, H., Kawaguchi, Y., Seino, S., Yokoi, N., Takeda, J., Inoue, I., Seino, Y., Yasuda, K., Hanafusa, T., Yamagata, K., Awata, T., Kadowaki, T., Hara, K., Yamada, N., Gotoda, T., Iwasaki, N., Iwamoto, Y., Sanke, T., Nanjo, K., Oka, Y., Matsutani, A., Maeda, E.and Kasuga, M.: "Association of the Pro12Ala substitution in peroxisome proliferator-activated receptor γ2 both with resistance to development of diabetes and with impairment of insulin secretion and disease severity in individuals with type 2 diabetes mellitus."Diabetes. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Abe, T., Yamaguchi, Y., Takino, H., Fujita, N., Yamauchi-Degawa, M., Ozaki, M., Yamakawa, K., Sera, Y., Sakamaki, H., Uotani, S., Kawasaki, E., Awata, T., Yamasaki, H.and Eguchi, K.: "CTLA4 gene polymorphism contributes to the mode of onset of diabetes with GAD antibody in Japanese patients : genetic analysis of diabetic patients with GAD antibody."Diabetic Med. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mori H et al.: "Association of the Pro12Ala substitution in peroxisome proliferator-activated receptor γ2 both with resistance to development of diabetes and with impairment of insulin secretion and disease severity in individuals with type 2 diabetes mellitus."Diabetes,. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Abe T et al.: "CTLA4 gene polymorphism contributes to the mode of onset of diabetes with GAD antibody in Japanese patients : genetic analysis of diabetic patients with GAD antibody."Diabetic Med,. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Chiba M et al.: "Tyrosine hydroxylase gene microsatellite polymorphism associated with insulin resistance in depressive disorder."Metabolism. 49. 1145-1149 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Awata T et al.: "Missense variations of the gene responsible for Wolfram syndrome (WFS1/wolframin) in Japanese : possible contribution of the Arg456His mutation to type 1 diabetes as a nonautoimmune genetic basis."Biochem Biophys Res Commun. 268. 612-616 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Awata T et al.: "Lack of association of the Ala45Thr variant in the BETA2/NE UROD1 with type 1 diabetes in Japanese."Diabetes Res Clin Pract. 49. 61-63 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Abe T et al.: "CTLA4 gene polymorphism correlates with the mode of onset and presence of ICA512 in Japanese Type 1 diabetes."Diabetes Res Clin Pract. 46. 169-175 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Abe,T.Awata,T.and Eguchi,K.: "CTLA-4 gene polymorphism determines the mode of onset of type 1 diabetes and presence of islet specific antibodies in Japanese patients"Diabetes Res Clin Pr.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Awata,T.Inoue,K.Inoue,I.et al.: "Lack of association of the Ala45Thr variant in the BETA2/NEURODI with type diabetes in Japanese"Diabetes Res Clin Pr.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Awata,T.Inoue,K.Kurihara.S.et al.: "Missense variations of the gene responsible for Wolfram syndrome(WFS1/wolframin)in Japanese: possible contribution of the Arg456His mutation to type 1 diabetes as a non-autoimmune genetic basis"Biochem Biophys Res Commun.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] 粟田卓也、栗原進、片山茂裕: "CTLA-4遺伝子と1型糖尿病。"分子糖尿病学の進歩1999(矢崎義雄監修、金原出版). 83-88 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 粟田卓也、井上清彰、片山茂裕: "1型糖尿病の疾患感受性遺伝子:診断法と診療への応用。"Pharm Medica. 17・9. 67-71 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 粟田卓也: "1型糖尿病の分子病態と発症遺伝子。"組織培養工学. 25・14. 562-566 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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