| Project/Area Number |
14013008
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | University of Tokyo |
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Principal Investigator |
KADOWAKI Takashi University of Tokyo Hospital, Department of Metabolic Diseases, Professor, 医学部附属病院糖尿病・代謝内科, 教授 (30185889)
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| Co-Investigator(Kenkyū-buntansha) |
HARA Kazuo University of Tokyo Hospital, Department of Metabolic Diseases, Assistant, 医学部附属病院糖尿病・代謝内科, 助手 (50359600)
YAMAUCHI Toshimasa University of Tokyo Hospital, Department of Metabolic Diseases, Special Associate Professor, 医学部附属病院糖尿病・代謝内科, 客員助教授 (40372370)
KUBOTA Naoto University of Tokyo Hospital, Department of Metabolic Diseases, Special Assistant, 医学部附属病院糖尿病・代謝内科, 客員助手 (50396719)
TOBE Kazuyuki University of Tokyo Hospital, Department of Metabolic Diseases, Special Assistant, 医学部附属病院糖尿病・代謝内科, 講師 (30251242)
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| Project Period (FY) |
2000 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥26,600,000 (Direct Cost: ¥26,600,000)
Fiscal Year 2004: ¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 2003: ¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 2002: ¥8,800,000 (Direct Cost: ¥8,800,000)
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| Keywords | SNP / Haplotype / diabetes / affected sib pair / adiponectin / 相関解析 / 連鎖不平衡 / インスリン抵抗性 / 2型糖尿病 / アディポネクチン受容体 / 脂肪細胞 / 個人情報匿名化 / 罹患同胞対法 / 全ゲノムスキャン / 一塩基多型 / 動脈硬化 |
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| Research Abstract |
We have mapped type 2 diabetes susceptibility genes to the 9 chromosomal regions 1p36-p32, 2q34, 3q26-q28, 6p23, 7p22-p21, 9p, llp13-p12, 15q13-q21, and 20q12-q13) in the Japanese population. In 3q26-q28, the gene encoding adiponectin which is adipocyte-derived insulin sensitizing hormone, is located. We found that SNP276 in the adiponectin gene was associated with plasma level of adiponectin, insulin resistance, and risk of type 2 diabetes, suggesting that the adiponectin gene is a type 2 diabetes susceptibility gene. In1q36-32, the AMPKa2 subunit gene is located ant we found that polymorphism in the AMPKa2 subunit gene is associated with insulin resistance and type 2 diabetes. In 20q12-q13 we found we found verystrong evidence of the association between type 2 diabetes and the haplotype consisting of two polymorphisms in the P2 promoter region of the HNF4A gene, although none of the individual polymorphisms examined showed any significant association with type 2 diabetes. In contrast, there was no association between type 2 diabetes and haplotypes consisting of polymorphisms not located in the P2 promoter region, suggesting that the type 2 diabetes susceptibility loci are localized in the P2 promoter region of the HNF4A gene. The results of the present analysis revealed that the HNF4A gene might be a type 2 diabetes susceptibility gene common to different ethnic groups. The study also suggested the possible existence of an as yet unidentified but functional polymorphism in the P2 promoter region of the HNF4A gene directly influencing the susceptibility to type 2 diabetes. We are performing association studies using dense map of SNP in the remaining 6 chromosomal regions we have mapped to identify type 2 diabetes susceptibility genes in the Japanese population.
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