Elucidation to Pathogenetic Mechanism of Nephrotic Proteinuria through Genetic and Functional Analysis
| Project/Area Number |
24390212
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NOIRI Eisei 東京大学, 医学部附属病院, 准教授 (00301820)
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| Co-Investigator(Kenkyū-buntansha) |
TOKUNAGA Katsushi 東京大学, 医学部, 教授 (40163977)
OKAMOTO Koji 東京大学, 医学部附属病院, 助教 (80572247)
DOI Kent 東京大学, 医学部附属病院, 助教 (80505892)
HAMASAKI Yoshifumi 東京大学, 医学部附属病院, 助教 (20617774)
NEGISHI Kosuke 東京大学, 医学部附属病院, 特任臨床医 (40572219)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
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| Keywords | ネフローゼ症候群 / 膜性腎症 / 糖尿病性腎症 / ゲノム解析 / HLA / ヘパラン硫酸プロテオグリカン / 蛋白尿 / 腎臓病学 / ヘパラン硫酸 / ゲノム医科学 |
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| Outline of Final Research Achievements |
Japan has 30,000 cases of intractable nephrotic syndrome (NS), which has a phenotype that is independent of pathological diagnosis. Recently, we found GPC5 and SULF2 from GWAS analysis of a Japanese NS cohort. Also, PLA2R1 and HLA-DQ1 are causal factors of primary NS. In this study, we generated BDF1 SULF2 deleted mice and subjected them to FGF2 and puromycin-induced mice NS. Results show that SULF2 plays a crucial protective role for proteinuria. GPC5 was also a susceptible gene in diabetic proteinuria. Genome-wide analysis of PLA2R1 found the new causal SNP in a Japanese cohort. HLA typing revealed the susceptible locus on NS. The interaction between PLA2R1 and HLA gene locus was found to have higher susceptibility to membranous nephropathy with odds ratio higher than 17. We are working now with the second cohort for validation. This project might prove the unique characteristics of Japanese NS cohort and elucidate the NS pathophysiology from the aspect of a common pathway on NS.
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Report
(4 results)
Research Products
(10 results)
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[Presentation] Sulfatase 2, Identified By Genome Association Analysis, Contributes to Protection against Nephrotic Syndrome2014
Author(s)
Kenjiro Honda, MD, PhD, Koji Okamoto, MD, PhD, Kent Doi, MD, PhD, FASN, Masaomi Nangaku, MD, PhD, Katsushi Tokunaga, Eisei Noiri, MD, PhD, FASN
Organizer
米国腎臓学会
Place of Presentation
フィラデルフィア会議場
Year and Date
2014-11-15
Related Report
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