2007 Fiscal Year Final Research Report Summary
Natural history of beta-cell destruction and accumulation of susceptible genes in type 1 diabetes
| Project/Area Number |
18591011
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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 |
Metabolomics
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| Research Institution | Okinaka Memorial Institute for Medical Research |
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Principal Investigator |
KOJI Nakanishi Okinaka Memorial Institute for Medical Research, Staff (80211423)
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| Project Period (FY) |
2006 – 2007
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| Keywords | type 1 diabetes / beta-cell function / HLA class I / HLA class II |
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| Research Abstract |
To elucidate the genetic factors contributing to heterogeneity of the rate of B-cell destruction in type 1 diabetes, we investigated the relationship between the time course of complete β-cell loss and HLA class I and II alleles. FHA allele frequencies were also examined among subgroups classified by the mode of onset. The subjects were 266 type 1 diabetic patients (among whom 196 patients were studied longitudinally) and 136 normal controls. Earlier complete loss of β-cell function was observed in patients who possessed both HLA-A24 and HLA-DQA1*03, as well as patients who had HLA-DR9, compared with those without Bleep HLA alleles (p=0.0057 and p=0.0093, respectively). Much earlier complete B-cell loss was observed in the patients who possessed all of HLA-A24, -DQA1*03, and -DR9 compared with the remaining patients (p=0.0011). The combination of HLA-A24, -DQA1*03, and -DR9 showed a higher frequency in acute-onset than slow-onset type 1 diabetes (p=0.0002). In contrast, HLA-DR2 was associated with a slower rate of progression to complete B-cell loss. These results indicate that the combination of HLA-A24, -DQA1*03, and -DR9 contributes to the acute onset and early complete β-cell destruction, while HLA-DR2 has a protective effect against complete β-cell loss in type 1 diabetes.
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