| Project/Area Number |
11470175
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Kitasato University |
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Principal Investigator |
MATSUURA Nobuo Kitasato Univ. School of Medicine, Department of Pediatrics, Professor, 医学部, 教授 (50002332)
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| Co-Investigator(Kenkyū-buntansha) |
KAZAHARI Kouji Kitasato Univ. School of Medicine, Department of Pediatrics, Research Associate, 医学部, 助手 (90214288)
NOMA Tsuyoshi Kitasato Univ. School of Medicine, Department of Pediatrics, Assistant Professor, 医学部, 講師 (60208387)
風張 真由美 北里大学, 医学部, 助手 (60224383)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1999: ¥3,700,000 (Direct Cost: ¥3,700,000)
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| Keywords | HLA antigen genes / DRβ genes / DQα genes / CTLA-4 gene / NeuroD / BETA2 gene / IDDMK_<1,2>-22 / Childhood diabetes / Qoβ gene / 発症感受性遺伝子 / HLA抗原遺伝子 / 1型糖尿病とQOL / IDDMK1,2-22遺伝子多型 / HbAlc値とQOL / BETA2遺伝子 / 遺伝子多型 / CD30遺伝子 / CD30Ligannd遺伝子 / 1型糖尿病の多様性 / 1型糖尿病 / SPIDDM / HLAclass II抗原遺伝子 / HLADQA遺伝子 / LHADQB遺伝子 / HLADRB遺伝子 |
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| Research Abstract |
1. HLA-DR, DQ beta genes and DQ alpha genes analysis
We analyzed HLA antigen genes in 146 patients with IDDM and 97 controls. The patients were divided into three groups, that is, group E, A, and S, depending on the age at onset and clinical course of the disease. We found significantly decreased frequency in DRB1 150X(D) in all diabetic groups, and increased in 0405(S), 0901(V) in groups in A and E.. Moreover, 0802(D) was significantly increased in group A. DQA1(301), DQB1(303), DRB1(901) genotype was found most susceptibility (RR=7.29 , 3.79, 2.82 in groups E, A, E respectively) in Japanese pat.
2. CTLA-4 and NeuroD/BETA2 polymorphism associated with Japanese childhood IDDM patients.: We found the significant increase in G/G phenotype, decreas A/A phenotype in group E compared with control. The relationship between HLA DRB1 405 and 901 and CTLA-4 polymorphism was evaluated. Odds ratio(OR) in 0901(+) vs 0901(-) and 0910(+)/CTLA4(G+) vs 0910(-)/CTLA4(G-) as well as 504 was significantly increased in diabetic groups suggested the both genes are additive but independently for the development of IDDM in Japanese children. There was no significant diference in NeuroD/BETA2 polymorphism in Japanese children.
3. Idenfication of nonsynonymous polymorphism in the superantigen(SPA)-coding region of IDDMK_<1,2>-22 and association with IDDM: We identified two nonsynony-mous A/G polymorphism at the 339- and 510- in the SPA-coding region of IDDM-K_<1,2>-22 retrovirus. We found significant G/G polymorphism at 510- in group E and G/A phenotype at 339- in group S. Future study will be necessary for conclusions.
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