| Project/Area Number |
15590956
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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 | The University of Tokyo (2004)
Tokyo Women's Medical University (2003) |
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Principal Investigator |
GOTODA Takanari The University of Tokyo, Faculty of Medicine, Visiting Associate Professor, 医学部附属病院, 客員助教授 (60322062)
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| Co-Investigator(Kenkyū-buntansha) |
KUSAKA Takako Tokyo Women's Medical University, Faculty of Medicine, Assistant, 医学部, 助手 (20338974)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | vitamine E / diabetes / complication / 遺伝子 / 血管合併症 |
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| Research Abstract |
We found that serum levels of α-and γ-tocopherol were significantly decreased in patients with diabetes mellitus as compared with non-diabetic subjects. A C-to-T polymorphism in intron 4 of the human α-tocopherol transfer protein (α-TTP) gene has been shown to be associated with serum tocopherol levels (T-allele associated with lower levels). We further screened the human α-TTP gene for gene mutation or gene variant, and identified a variable number (9〜12) of adenine nucleotide repeat located 335 nucleotides upstream of the putative transcription initiation site. The allelic frequency of the -335A(n) polymorphism was as follows ; A(10)>A(11)>>A(9), A(10). Both the intron 4 C/T polymorphism and the -335A(n) polymorphism were almost in tight linkage disequilibrium, with the T-allele linked to the A(11)-allele. Luciferase promoter assay in 293 cells revealed that the reporter construct containing the A(11)-allele had significantly lower promoter activity than that containing the A(10)-allele. Among diabetic patients, the T-allele, and therefore the A(11)-allele as well, have been shown to be associated with occurrence of diabetic retinopathy [OR=1.76 (95%CI : 1.03-2.89). These results encourage further investigation about possible association between α-TTP and diabetic complications.
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