1997 Fiscal Year Final Research Report Summary
Analysis of IDDM susceptibility genes with family-based association studies.
| Project/Area Number |
08671180
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内分泌・代謝学
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| Research Institution | Saitama Medical School |
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Principal Investigator |
AWATA Takuya The Fourth Department of Internal Medicine, Saitama Medical School, Instructor, 医学部, 講師 (40184303)
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| Project Period (FY) |
1996 – 1997
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| Keywords | lDDM / Susceptibility / Insulin gene / CTLA-4 / IL-1 / VNTR / Polymorphism |
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| 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.
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[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
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[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
