International collaboration on the research of novel urate transporters by leveraging genetic differences between the Japanese and the Czech
| Project/Area Number |
18KK0247
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| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TAKADA Tappei 東京大学, 医学部附属病院, 講師 (90376468)
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| Co-Investigator(Kenkyū-buntansha) |
市田 公美 東京薬科大学, 薬学部, 教授 (80183169)
松尾 洋孝 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 分子生体制御学, 准教授 (00528292)
豊田 優 東京大学, 医学部附属病院, 届出研究員 (80650340)
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| Project Period (FY) |
2018-10-09 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2020: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2019: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2018: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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| Keywords | 尿酸 / 遺伝子多型 / トランスポーター / 人種差 / 国際共同研究 |
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| Outline of Final Research Achievements |
By a series of in vitro experiments and clinical analyses including international collaborations, we revealed that 1) there were clinically-relevant rare dysfunctional variants of ABCG2 in a gout and hyperuricemia cohort, 2) there were novel loci which aggravate asymptomatic hyperuricemia into gout revealed by genome-wide association studies, 3) familial early-onset hyperuricemia and gout associated with dysfunctional variants of ABCG2, 4) there were subtype-specific gout susceptibility loci and enrichment of selection pressure on ABCG2 and ALDH2 identified by subtype genome-wide meta-analyses of clinically defined gout patients.
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| Academic Significance and Societal Importance of the Research Achievements |
本国際共同研究で得られた研究成果は、痛風、高尿酸血症をはじめとするさまざまな尿酸関連疾患の予防・治療戦略の立案に役立つことが期待される。例えば、より精度の高い遺伝子診断による各種疾患のリスク予測などに貢献しうるものであり、今後、応用研究や社会実装も見据えた研究のさらなる発展が期待される。
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Report
(4 results)
Research Products
(45 results)
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[Journal Article] Identification of GLUT12/SLC2A12 as a urate transporter that regulates the blood urate level in hyperuricemia model mice.2020
Author(s)
Toyoda Y, Takada T, Miyata H, Matsuo H, Kassai H, Nakao K, Nakatochi M, Kawamura Y, Shimizu S, Shinomiya N, Ichida K, Hosoyamada M, Aiba A, Suzuki H
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Journal Title
Proc. Natl.Acad. Sci. USA
Volume: 117
Issue: 31
Pages: 18175-18177
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Higher Blood Uric Acid in Female Humans and Mice as a Protective Factor Against Pathophysiological Decline of Lung Function2020
Author(s)
Fujikawa H, Sakamoto Y, Masuda N, Oniki K, Kamei S, Nohara H, Nakashima R, Maruta K, Kawakami T, Eto Y, Takahashi N, Takeo T, Nakagata N, Watanabe H, Otake K, Ogata Y, Tomioka NH, Hosoyamada M, Takada T, Ueno-Shuto K , Suico MA, Kai H, Saruwatari J, Shuto T.
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Journal Title
Antioxidants
Volume: 9
Issue: 5
Pages: 387-387
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A common variant of LDL receptor related protein 2 (LRP2) gene is associated with gout susceptibility: a meta-analysis in a Japanese population.2020
Author(s)
Akashi A, Nakayama A, Kamatani Y, Higashino T, Shimizu S, Kawamura Y, Imoto M, Naito M, Hishida A, Kawaguchi M, Takao M, Matsuo M, Takada T, Ichida K, Ooyama H, Shinomiya N, Matsuo H.
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Journal Title
Hum Cell.
Volume: 33
Issue: 2
Pages: 303307-303307
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Dysfunctional missense variant of OAT10/SLC22A13 decreases gout risk and serum uric acid levels.2020
Author(s)
Higashino T, Morimoto K, Nakaoka H, Toyoda Y, Kawamura Y, Shimizu S, Nakamura T, Hosomichi K, Nakayama A, Ooyama K, Ooyama H, Shimizu T, Ueno M, Ito T, Tamura T, Naito M, Nakashima H, Kawaguchi M, Takao M, Kawai Y, Osada N, Ichida K, Yamamoto K, Suzuki H, Shinomiya N, Inoue I, Takada T, Matsuo H.
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Journal Title
Ann Rheum Dis.
Volume: 79(1)
Issue: 1
Pages: 164-166
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Functional Characterization of Clinically-Relevant Rare Variants in ABCG2 Identified in a Gout and Hyperuricemia Cohort2019
Author(s)
Toyoda Yu, Mancikova Andrea, Krylov Vladimir, Morimoto Keito, Pavelcova Katerina, Bohata Jona, Pavelka Karel, Pavlikova Marketa, Suzuki Hiroshi, Matsuo Hirotaka, Takada Tappei, Stiburkova Blanka
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Journal Title
Cells
Volume: 8
Issue: 4
Pages: 363-363
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Identification of ABCG2 as an Exporter of Uremic Toxin Indoxyl Sulfate in Mice and as a Crucial Factor Influencing CKD Progression.2018
Author(s)
Takada T, Yamamoto T, Matsuo H, Tan JK, Ooyama K, Sakiyama M, Miyata H, Yamanashi Y, Toyoda Y, Higashino T, Nakayama A, Nakashima A, Shinomiya N, Ichida K, Ooyama H, Fujimori S, Suzuki H
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Journal Title
Scientific Reports
Volume: 8
Issue: 1
Pages: 11147-11147
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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