Model analysis focusing on the mechanisms of rare variants in IgA nephropathy

• Project/Area Number: 15K09250
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Niigata University
• Principal Investigator: Goto Shin 新潟大学, 医歯学系, 准教授 (00463969)
• Co-Investigator(Kenkyū-buntansha): 成田 一衛 新潟大学, 医歯学系, 教授 (20272817)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: IgA腎症 / エクソーム解析 / 口蓋扁桃 / リシークエンス / 遺伝子変異

Outline of Final Research Achievements

IgA nephropathy (IgAN) is the most prevalent glomerulonephritis among worldwide. Because familial aggregation is observed, genetic factors could be involved in the development of IgAN. We have collected 30 familial IgAN samples, and have carried out comprehensive genomic analysis. Among variants detected by next generation sequencer, multiple rare variants related to immune cells or mucosal immunity are co-segregated with patients in multiplex families.
Next, we have conducted the quantitative analysis of galactose-deficient IgA1 (Gd-IgA1), APRIL, and IgA repertoire in palatine tonsils removed to treat IgAN. The levels of Gd-IgA1 were correlated with the degree of deposition of Gd-IgA1 in glomerulus, and usage of some V gene in IgA were defferent from that of controls, and this analysis is still ongoing.

Research Products

• [Journal Article] Comprehensive microbiome analysis of tonsillar crypts in IgA nephropathy (2017)
  • Author(s): Watanabe H, Goto S, Mori H, Higashi K, Hosomichi K, Aizawa N, Takahashi N, Tsuchida M, Suzuki Y, Yamada T, Horii A, Inoue I, Kurokawa K, Narita I.
  • Journal Title: Nephrol Dial Transplant Volume: in press Pages: 2072-2079
  • DOI: 10.1093/ndt/gfw343
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comparison of methods of steroid administration combined with tonsillectomy for IgA nephropathy patients (2016)
  • Author(s): Watanabe H, Goto S, Kondo D, Takata T, Yamazaki H, Hosojima M, Yamamoto S, Kaneko Y, Aoyagi R, Narita I.
  • Journal Title: Clin Exp Nephrol Volume: in press Issue: 2 Pages: 257-265
  • DOI: 10.1007/s10157-016-1282-8
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 家族性IgA腎症候補遺伝子を対象としたレアバリアント関連解析 (2017)
  • Author(s): 後藤 眞
  • Organizer: 第60回日本腎臓学会学術総会
• [Presentation] Comprehensive microbiome analysis of tonsillar crypts in IgA nephropathy (2015)
  • Author(s): Hirofumi Watanabe, Shin Goto, Masafumi Tsuchida, Ichiei Narita
  • Organizer: 2015 Kidney Week (Annual conference of American Society of Nephrology)
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-11-05
• [Presentation] エクソーム解析と連鎖解析による IgA腎症関連遺伝子変異の検出 (2015)
  • Author(s): 後藤眞、塚口裕康、渡辺博文、土田雅文、福田顕弘、藤本昭一、成田一衞
  • Organizer: 第58回日本腎臓学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-06-07