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Analysis of IDDM susceptibility genes with family-based association studies.

Research Project

Project/Area Number 08671180
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionSaitama Medical School

Principal Investigator

AWATA Takuya  The Fourth Department of Internal Medicine, Saitama Medical School, Instructor, 医学部, 講師 (40184303)

Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
KeywordslDDM / Susceptibility / Insulin gene / CTLA-4 / IL-1 / VNTR / Polymorphism
Research Abstract

We analyzed the variable number of tandem repeats (VNTR) in the 5' region of the insulin gene, the CTLA-4 gene polymorphisms and the polymorphisms of IL-1 gene cluster to assess their roles in IDDM development.
1. Insulin gene VNTR (IDDM2)
Although the shortest (class 1) VNTR alleles in the 5' region of the insulin gene are positively associated with IDDM in Caucasians, majority of Japanese are homozygous for class 1 alleles. We analyzed precisely class 1 alleles in Japanese. The shortest component i.e. 1S alleles (25-38 RUs) were significantly increased in the IDDM group compared with the control group. The lS/1S genotype was significantly increased in the Patients (P=0.005, relative risk 2.1). Furthermore, the transmission disequilibrium test of Japanese families with lS/1M or lS/1L heterozygous parents confirmed the association of lS a11eles. The present study suggests that a class 1 subset may have a role in IDDM susceptibility in Japan.
2. CTLA-4 gene polymorphisms (IDDM12)
The frequency of the G allele of the CTLA-4 polymorphism was significantly high in autoirmmume thyroid disease (AITD) patients than in control subjects. In contrast, the G allele was not significantly associated with IDDM.However, the frequency of the G a11ele was signiiicantly high in patients with both acute onset (defined by insulin requirement <less than or equal> 1 month after onset) and insulin-depletion (defined by postprandial serum C-peptide < 0.033 nmo1/l) than in control subjects. The present results suggest that CTLA-4 gene polymorphism contributes to a common autoimmune process in IDDM and autoimmune thyroid dis
3. IL-1 gene cluster polymorphisms
Significant associations of IL-1 gene cluster polymorphisms (IL-1beta and IL1R1) with IDDM or AITD were not observed. Thus, in Japanese, the IL-1 gene region appears to be insignificant in susceptibility to IDDM or AITD.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Awata, T.: "Evidence for assaoiation between the class I subset of the insnlin gene minisatellite(IDDM2 locus)and IDDM in the Japanese population." Diabetes. 46(10). 1637-1642 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Awata, T.: "Association of CTLA-4 gene A-G polymorphism(IDDM12 locus)with acute-on set and insulin-depleted IDDM as well as autoimmune thyroid disease…" Diabetes. 47(1). 128-129 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 粟田 卓也: "IDDM発症遺伝子IDDM2(インスリン遺伝子上流繰り返し配列)の日本人における検討:配列の多様性とIDDMとの関連" 分子糖尿病学. 8. 145-149 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 粟田 卓也: "インスリン遺伝子上流繰返し配列(VNTR)" 日本臨床(糖尿病1). 増刊. 376-281 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 粟田 卓也: "IDDMの成因に関する最近の進歩-インスリン遺伝子上流繰返し配列" 内分泌・糖尿病科. 6(1). 20-25 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Awata, T., Kurihara, S., Kikuchi, C., Takei, S., Inoue, I., IShii, C., Takahashi, K., Negishi, K., Yshida, Y., Hagura, R,Kanazawa, Y.and Katayama, S.: "Evidence for association between the class I Subset of insulin gene minisatellite (IDDM2 locus) and IDDM in the Japanese population." Diabetes. 46(10). 1637-1642 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Awata, T., Kurihara, S., Iitaka, M., Takei, S., Inoue, I., Ishii, C., Negishi, K., Izumida, T., Yoshida, Y., Hagura, R., Kuzuya, N., Kanazawa, Y.and Katayama, S.: "Association of CTLA-4 gene A-G polymorphism (IDDM12 locus) with acute-onset and insulin-depleted IDDM as well as autoimmune thyroid disease (Graves' disease and Hashimoto's thyroiditis) in the Japanese population" Diabetes. 47(1). 128-129 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Awata,T: "Evidence for association between the classI subset of the insulin gene minisatellite(IDDM2 locus)and IDDM in the Japanese population." Diabetes. 46(10). 1637-1642 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Awata,T: "Association of CTLA-4 gene A-G polymorphism(IDDM12 locus)with acute-orset and insulin-depleted IDDM as well as autoimmune thyroid clisease…" Diabetes. 47(1). 128-129 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 粟田 卓也: "IDDM発症遺伝子 IDDM2(インスリン遺伝子上流繰り返し配列)の日本人における検討;配列の多様性とIDDMとの関連" 分子糖尿病学. 8. 145-149 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 粟田 卓也: "インスリン遺伝子上流繰り返し配列(VNTR)" 日本臨床(糖尿病1). 増刊. 376-381 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 粟田 卓也: "IDDMの成因に関する最近の進歩ーインスリン遺伝子上流繰り返し配列" 内分泌・糖尿病科. 6(1). 20-25 (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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