2005 Fiscal Year Final Research Report Summary
Identification of type 2 diabetes susceptibility genes in the Japanese population by linkage disequilibrium mapping in the chromosomal regions harboring type 2 diabetes susceptibility genes
| Project/Area Number |
15310138
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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 |
Applied genomics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HARA Kazuo The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (50359600)
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| Co-Investigator(Kenkyū-buntansha) |
KADOWAKI Takashi The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (30185889)
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| Project Period (FY) |
2003 – 2005
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| Keywords | SNP / Haplotype / diabetes / affected sib pair / adiponectin |
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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, 11p13p-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. In 1q36-32, the AMPKα2 subunit gene is located ant we found that polymorphism in the AMPKα2 subunit gene is associated with insulin resistance and type 2 diabetes. In 20q12-q13 we found we found very strong 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, therse 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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[Journal Article] Absence of an association between the polymorphisms in the genes encoding adiponectin receptors and type 2 diabetes.2005
Author(s)
Hara K, Horikoshi M, Kitazato H, Yamauchi T, Ito C, Noda M, Ohashi J, Froguel P, Tokunaga K, Nagai R, Kadowaki T.
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Journal Title
Diabetologia 48
Pages: 1307-1314
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression of DGAT2 in white adipose tissue is regulated by central leptin action.2005
Author(s)
Suzuki R, Tobe K, Aoyama M, Sakamoto K, Ohsugi M, Kamei N, Nemoto S, Inoue A, Ito Y, Uchida S, Hara K, Yamauchi T, Kubota N, Terauchi Y, Kadowaki T.
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Journal Title
J.Biol.Chem. 280
Pages: 3331-3337
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Insulin/Foxol pathway regulates expression levels of adiponectin receptors and adiponectin sensitivity.2004
Author(s)
Tsuchida A, Yamauchi T, Ito Y, Hada Y, Maki T, Takekawa S, Kamon J, Kobayashi M, Suzuki R, Hara K, Kubota N, Terauchi Y, Froguel P, Nakae J, Kasuga M, Accili D, Tobe K, Ueki K, Nagai R, Kadowaki T.
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Journal Title
J.Biol.Chem. 279
Pages: 30817-30822
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin.2003
Author(s)
Waki H, Yamauchi T, Kamon J, Ito Y, Uchida S, Kita S, Hara K, Hada Y, Vasseur F, Froguel P, Kimura S, Nagai R, Kadowaki T.
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Journal Title
J.Biol.Chem. 278
Pages: 40352-40363
Description
「研究成果報告書概要(欧文)」より
