Analysis of Candidate Genes within a New Disease Locus in Asian Patients with Steroid Resistance Nephrotic Syndrome

2008 Fiscal Year Final Research Report

• Project/Area Number: 19590953
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kansai Medical University (2008); The University of Tokushima (2007)
• Principal Investigator: TSUKAGUCHI Hiroyasu Kansai Medical University, 医学部, 助教 (60335792)
• Co-Investigator(Kenkyū-buntansha): DOI Toshio 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (60183498)
• Project Period (FY): 2007 – 2008
• Keywords: ポドサイト / 腎不全 / ネフローゼ症候群

Research Abstract

Steroid resistance nephrotic syndrome, characterized by renal histology of focal segmental glomerulosclerosis, is a leading cause of childhood end-stage renal failure. There are a significant ethnic difference in genetic factors underlying autosomal recessive, familial SRNS. Linkage mapping with 17 Asian SRNS families demonstrated a new disease locus with a multi-point LOD score of 5.8 (α=0.7, manuscript in preparation). The candidate interval spans about 3.5Mb, which contains～50 genes. We are currently doing mutational analysis of candidate genes, particularly focusing on those which are specifically enriched in glomeruli

Research Products

• [Journal Article] Glomerular proteins related to slit diaphragm and matrix adhesion in the foot processes are highly tyrosine phosphorylated in the normal rat kidney (2010)
  • Author(s): Zhang Y, Yoshida Y, Nameta M, Xu B, Taguchi I, Ikeda T, Fujinaka H, Mohamed SM, Tsukaguchi H, Harita Y, Yaoita E, Yamamoto T.
  • Journal Title: Nephrol Dial Transplant (Epub ahead of print)
• [Journal Article] Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis (2010)
  • Author(s): Brown EJ, Schlondorff JS, Becker DJ, Tsukaguchi H, Uscinski AL, Higgs HN, Henderson JM, Pollak MR
  • Journal Title: Nat Genet 42(1) Pages: 72-76
• [Journal Article] Phosphorylation of nephrin triggers its internalization by raft-mediated endocytosis (2009)
  • Author(s): Qin XS, Tsukaguchi H, Shono A, Yamamoto A, Kurihara H, Doi T.
  • Journal Title: J Am Soc Nephrol 20(12) Pages: 2534-2545
• [Journal Article] Predisposition to relapsing nephrotic syndrome by a nephrin mutation that interferes with assembly of functioning microdomains (2009)
  • Author(s): Shono A, Tsukaguchi H, Kitamura A, Hiramoto R, Qin XS, Doi T, Iijima K.
  • Journal Title: Hum Mol Genet 18(16) Pages: 2943-2956
• [Journal Article] Toll-like receptor 9 affects severity of IgA nephropathy (2008)
  • Author(s): Suzuki H, Suzuki Y, Narita I, Aizawa M, Kihara M, Yamanaka T, Kanou T, Tsukaguchi H, Novak J, Horikoshi S, Tomino Y.
  • Journal Title: J Am Soc Nephrol 19(12) Pages: 2384-2395
• [Journal Article] Steroid-resistant nephrotic syndrome (2008)
  • Author(s): Kitamura A, Tsukaguchi H, Maruyama K, Shono A, Iijima K, Kagami S, Doi T.
  • Journal Title: Kidney Int 74(9) Pages: 1209-1215
• [Journal Article] Increase of integrin-linked kinase activity in cultured podocytes upon stimulation with plasma from patients with recurrent FSGS (2008)
  • Author(s): Hattori M, Akioka Y, Chikamoto H, Kobayashi N, Tsuchiya K, Shimizu M, Kagami S, Tsukaguchi H.
  • Journal Title: Am J Transplant 8(7) Pages: 1550-1556
• [Journal Article] Clinical features and mutational survey of NPHS2 (podocin) in Japanese children with focal segmental glomerulosclerosis who underwent renal transplantation (2008)
  • Author(s): Furue T, Hattori M, Tsukaguchi H, Kitamura A, Oomori T, Ogino D, Nakakura H, Ashida A, Miura K, Hisano M, Takahashi K, Chikamoto H, Akioka Y, Sakano T.
  • Journal Title: Pediatr Transplant 12(3) Pages: 341-346
• [Journal Article] Podocin participates in the assembly of tight junctions between foot processes in nephrotic podocytes (2007)
  • Author(s): Shono A, Tsukaguchi H, Yaoita E, Nameta M, Kurihara H, Qin XS, Yamamoto T, Doi T.
  • Journal Title: J Am Soc Nephrol 18(9) Pages: 2525-2533
• [Presentation] ネフローゼ症候群研究の新たな展開ネフローゼ症候群遺伝子研究の最近の知見ポドサイト遺伝子の重要性 (2009)
  • Organizer: 第52回日本腎臓学会総会シンポジウムS1-1-1
  • Place of Presentation: 横浜 (パシフィコ横浜)
  • Year and Date: 2009-06-03