1987 Fiscal Year Final Research Report Summary
Study of the Pathogenesis of Type I Diabetes Mellitus by The Analysis of Human Major Histocompatibility Complex Antigen
| Project/Area Number |
60480265
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | The 3er Department of Internal Medicine, Faculty of Medicine, University of Tokyo |
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Principal Investigator |
KANAZAWA Yasunori Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 医学部(病), 講師 (10010399)
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| Co-Investigator(Kenkyū-buntansha) |
AWATA Takuya Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 医学部(病), 医員 (40184303)
SHIBASAKI Yoshikazu Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 医学部(病), 助手 (80196419)
OKA Yoshitomo Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 医学部(病), 助手 (70175256)
JUJI Takeo Division of blood Transfusion Service, Department of Medicine, Faculty of Medici, 医学部(病), 教授 (20009997)
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| Project Period (FY) |
1985 – 1987
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| Keywords | Type I Diabetes Mellitus / HLA / DNA / Restriction Endonuclease / Southern-Hybridization / HLA-DQB gene / Relative Risk / Riskfactor / Insulin gene / NODマウス |
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| Research Abstract |
The risk factor of diabetes mellitus has been investigated at the level of (1), insulin gene, (2) insulin receptor gene(s), (3) HLA genes. The interest has been focusted ot the relationship between type I diabetes and HLA types, since autoimmune nature of the pathogenesis of type I diabetes has been reported in Erope and in United States. However, the level of relative risk obtained form ceratin HLA types were low, at most 8 times of those who had not that HLA type. Some of these researchers stated that analysis of HLA genes could give us much higher relative risk for diabetes.
Our study on HLA genes of Japanese type I diabetes was urgent by two reasons (1) low incidence of type I diabetes in Japaneses than those of Caucasian (at least 10 times less) (2) very different HLA patterns of Japanese comparing to Caucasians. Patients have been selected, because they have Characteristics of typical type I diabetes. Non-diabetic control subjects have been chosen from healthy persons who do not h
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ave any familial releation with selected patients and who do not have any family history of type I diabetes. DR 4 and DR 9 had significant but not so high relative risk in our examination by serological test.
High molecular DNA were extracted from those patients and control subjects and were digested with several different endonucleases. Southern-hybridization analyses using HLA-DQB gene probe proved that there were highly significant difference of the incidence of Bam HI Fragments os 4.5, 4.9, 5.6 kb. These results are diferent from those observed in Cancasian and therefore characteristic nature of HLA in Japanese type I diabetics.
Summing up these results and comparing with those obtained with Cancasians, HLA-DQB gene is an important factor in the pathogenesis of type I diabetes.
In pallarel with those HLA gene studies, we examined several factors which might relate to the pathogenesis of type I diabetes. Those were polymorphism of 5' end flanking region of insulin gene and one of the representative animal model of type I diabetes: NOD mouse. Our studies accumulated the information of athogenesis of type I diabetes. However, further studies may need to elucidate the real mechanism(s). Less
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