Identifying the genetic causality of familial IgAN by a new analysis system

2013 Fiscal Year Final Research Report

• Project/Area Number: 23659441
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Niigata University
• Principal Investigator: NARITA Ichiei 新潟大学, 医歯学系, 教授 (20272817)
• Co-Investigator(Kenkyū-buntansha): GOTO Shin 新潟大学, 医歯学系, 講師 (00463969)
• Project Period (FY): 2011 – 2013
• Keywords: IgA腎症 / ゲノム / 連鎖解析

Research Abstract

To identify the genetic causality of familial IgAN, we applied exome sequencing to a family comprising four biopsy-proven IgAN patients. Genome-wide linkage analysis was concurrently carried out. Thirteen variants which were shared only by affected individuals in the family were selected as candidate genes for familial IgAN. Linkage analysis of the family revealed linkage signals at nine loci, and among the candidates, a novel missense variant F161Y in EEA1, encoding Early Endosome Antigen 1. Furthermore, the F161Y variant completely co-segregated in the family and this variant is existed in the highly conserved region across zebrafish to human. Resequence analysis of EEA1 revealed that among additional 27 familial IgAN, six families carried the other three variants within EEA1. Frequencies of these EEA1 variants in familial IgAN was significantly higher than those in The Human Genetic Variation Database, indicating that EEA1 gene is a susceptibility gene for Japanese familial IgAN.

Research Products

• [Journal Article] Expression of tight junction protein claudin-1 in human crescentic glomerulonephritis (2014)
  • Author(s): Koda R, Yoshino A, manishi Y, Kawamoto S, Ueda Y, Yaoita E, Kazama JJ, Narita I, Takeda T
  • Journal Title: Intern J Nephrol Volume: (Epub)
  • Peer Reviewed
• [Journal Article] Role of the p.E66Q variant of GLAin the progression of chronic kidney disease (2014)
  • Author(s): WatanabeH, Goto S, Miyashita A, Maruyama H, Wakasugi M, Yokoseki A, Kuwano R, Narita I
  • Journal Title: Clin Exp Nephrol Volume: (Epub)
  • Peer Reviewed
• [Journal Article] High rates of death and hospitalization follow bone fracture among hemodialysis patients (2014)
  • Author(s): Wakasugi M, Kazama JJ, Narita I
  • Journal Title: Kidney Int Volume: (in press)
  • Peer Reviewed
• [Journal Article] Association of warfarin use and incidence of ischemic stroke in Japanese hemodialysis patients with chronic sustained atrial fibrillation : A prospective cohort study (2014)
  • Author(s): Wakasugi M, Kazama JJ, Narita I, et al.
  • Journal Title: Clin Exp Nephrol Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Upregulation of prolactin receptor in proximal tubular cells was induced in cardiac dysfunction model mice (2014)
  • Author(s): Tsuchida Y, Kaneko Y, Otsuka T, Goto K, Saito A, Yamamoto K, Yamamoto T, Narita I
  • Journal Title: Clin Exp Nephrol Volume: 18 Pages: 65-74
  • Peer Reviewed
• [Journal Article] Effect of donor-recipient age difference on long-term graft survival in living kidney transplantation (2014)
  • Author(s): Tasaki M, Saito K, Nakagawa Y, Ikeda M, Imai N, Narita I, Takahashi K
  • Journal Title: International Urology and Nephrology Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Budget impact analysis of chronic kidney disease mass screening test in Japan (2014)
  • Author(s): Kondo M, Yamagata K, Hoshi SL, Saito C, Asahi K, Moriyama T, Tsuruya K, Konta T, Fujimoto S, Narita I, Kimura K, Iseki K, Watanabe T
  • Journal Title: Clin Exp Nephrol Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Assessment of interleukin-6 receptor inhibition therapy on periodontal condition in patients with rheumatoid arthritis and chronic periodontitis (2014)
  • Author(s): Kobayashi T, Okada M, Ito S, Kobayashi D, Ishida K, Kojima A, Narita I, Murasawa A, Yoshie H
  • Journal Title: J Periodontol Volume: 85 Pages: 57-67
  • Peer Reviewed
• [Journal Article] A hip fracture in a dialysis patient with Abeta2M amyloidosis (2014)
  • Author(s): Kazama JJ, Yamamoto S, Wakasugi M, Narita I
  • Journal Title: Kidney Int Volume: 85 Pages: 214-5
  • Peer Reviewed
• [Journal Article] A combination of healthy lifestyle factors is associated with a decreased incidence of chronic kidney disease : a population-based cohort study (2013)
  • Author(s): Wakasugi M, Kazama JJ, Yamamoto S, Kawamura K, Narita I
  • Journal Title: Hypertens Res Volume: 36 Pages: 328-33
  • Peer Reviewed
• [Journal Article] Cause-specific excess mortality among dialysis patients : comparison with the general population in Japan (2013)
  • Author(s): Wakasugi M, Kazama JJ, Yamamoto S, Kawamura K, Narita I
  • Journal Title: Ther Apher Dial Volume: 17 Pages: 298-304
  • Peer Reviewed
• [Journal Article] Increased risk of hip fracture among Japanese hemodialysis patients (2013)
  • Author(s): Wakasugi M, Kazama JJ, Taniguchi M,Wada A, Iseki K, Tsubakihara Y, Narita I
  • Journal Title: J Bone Miner Metab Volume: 31 Pages: 315-21
  • Peer Reviewed
• [Journal Article] Two Susceptibility Loci to Takayasu Arteritis Reveal a Synergistic Role of the IL12B and HLA-B Regions in a Japanese Population (2013)
  • Author(s): Terao C, Yoshifuji H, Kimura A, Matsumura T, Ohmura K, Takahashi M, Shimizu M,Kawaguchi T, Chen Z, Naruse TK, Sato-Otsubo A, Ebana Y, Maejima Y, Kinoshita H, Murakami K, Kawabata D, Wada Y, Narita I, Tazaki J, Kawaguchi Y, Yamanaka H, Yurugi K, Miura Y, Maekawa T, Ogawa S, Komuro I, Nagai R, Yamada R, Tabara Y, Isobe M, Mimori T, Matsuda F
  • Journal Title: AmJ HumGenet Volume: 93 Pages: 289-97
  • Peer Reviewed
• [Journal Article] The clinical course of patients with IgG4-related kidney disease (2013)
  • Author(s): Saeki T, Kawano M, Mizushima I, Yamamoto M, Wada Y, Nakashima H, Homma N, Tsubata Y, Takahashi H, Ito T, Yamazaki H, Saito T, Narita I
  • Journal Title: Kidney Int Volume: 84 Pages: 826-33
  • Peer Reviewed
• [Journal Article] Screening of male dialysis patients for fabry disease by plasma globotriaosylsphingosine (2013)
  • Author(s): Maruyama H, Takata T, Tsubata Y, Tazawa R, Goto K, Tohyama J, Narita I, Yoshioka H, Ishii S
  • Journal Title: Clin J Am Soc Nephrol Volume: 8 Pages: 629-36
  • Peer Reviewed
• [Journal Article] Distribution of amyloid deposits in the kidneys of a patient with reactive amyloidosis associated with rheumatoid arthritis (2013)
  • Author(s): Kuroda T, Tanabe N, Sato H, Nakatsue T, Wada Y, Murakami S, Nakano M, Narita I
  • Journal Title: BMC research notes Volume: 6 Pages: 231
  • Peer Reviewed
• [Journal Article] DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked is an immunogenic target of cancer stem cells (2013)
  • Author(s): Koshio J, Kagamu H, Nozaki K, Saida Y, Tanaka T, Shoji S, Igarashi N, Miura S, Okajima M, Watanabe S, Yoshizawa H, Narita I
  • Journal Title: Cancer Immunol Immunother Volume: 62 Pages: 1619-28
  • Peer Reviewed
• [Journal Article] A case of Epstein-Barr virus-related lymphadenopathy mimicking the clinical features of IgG4-related disease (2013)
  • Author(s): Wada Y, Kojima M, Yoshita K, Yamazaki M, Kobayashi D, Murakami S, Nishi S, Nakano M, Narita I
  • Journal Title: Mod Rheumatol Volume: 23 Pages: 597-603
  • Peer Reviewed
• [Journal Article] Significance of urinary full-length and ectodomain forms of megalin in patients with type 2 diabetes (2012)
  • Author(s): Ogasawara S, Hosojima M, Kaseda R, Kabasawa H, Yamamoto-Kabasawa K, Kurosawa H, Sato H, Iino N, Takeda T, Suzuki Y, Narita I, Yamagata K, Tomino Y, Gejyo F, Hirayama Y, Sekine S, Saito A
  • Journal Title: Diabetes Care Volume: 35 Pages: 1112-8
  • Peer Reviewed
• [Journal Article] Integrin alpha1/beta1 and alpha2/beta1 as a receptor for IgA1 in human glomerular mesangial cells in IgA nephropathy (2012)
  • Author(s): Kaneko Y, Otsuka T, Tsuchida Y, Gejyo F, Narita I
  • Journal Title: Int Immunol Volume: 24 Pages: 219-32
  • Peer Reviewed
• [Journal Article] Geographic Differences in Genetic Susceptibility to IgA Nephropathy : GWAS Replication Study and Geospatial Risk Analysis (2012)
  • Author(s): Kiryluk K, Li Y, Sanna-Cherchi S, Rohanizadegan M, Suzuki H, Eitner F, Snyder HJ, Narita I, Berthoux F, Floege J, Stengel B, Zhang H, Lifton RP, Gharavi AG
  • Journal Title: PLoS Genet Volume: 8 Pages: e1002765
  • Peer Reviewed
• [Journal Article] Differences in the local and national prevalences of chronic kidney disease based on annual health check program data (2012)
  • Author(s): Wakasugi M, Kazama JJ, Narita I
  • Journal Title: Clinl Exp Nephrol Volume: 16 Pages: 749-54
  • Peer Reviewed
• [Journal Article] Depletion of radio-resistant regulatory T cells enhances antitumor immunity during recovery from lymphopenia (2012)
  • Author(s): Baba J,Watanabe S, Saida Y, Tanaka T, Miyabayashi T, Koshio J, Ichikawa K, Nozaki K, Koya T, Deguchi K, Tan C, Miura S, Tanaka H, Tanaka J, Kagamu H, Yoshizawa H, Nakata K, Narita I
  • Journal Title: Blood Volume: 120 Pages: 2417-27
  • Peer Reviewed
• [Journal Article] Use of Japanese Society for Dialysis Therapy dialysis tables to compare the local and national incidence of dialysis (2012)
  • Author(s): Wakasugi M, Kazama JJ, Narita I
  • Journal Title: Ther Aphe Dial Volume: 16 Pages: 63-7
  • Peer Reviewed
• [Journal Article] Light-microscopic characteristics of IgG4-related tubulointerstitial nephritis : distinction from non-IgG4-related tubulointerstitial nephritis (2012)
  • Author(s): Yoshita K, Kawano M, Mizushima I, Hara S, Ito Y, Imai N, Ueno M, Nishi S, Nomura H, Narita I, Saeki T
  • Journal Title: Nephrol Dial Transpl Volume: 27 Pages: 2755-61
  • Peer Reviewed
• [Journal Article] Quantitative Histological Analysis of SM22alpha (Transgelin) in an Adriamycin-Induced Focal Segmental Glomerulosclerosis Model (2012)
  • Author(s): Wang X, Sakatsume M, Sakamaki Y, Inomata S, Yamamoto T, Narita I
  • Journal Title: Nephron Exp Nephrol Volume: 120 Pages: e1-e11
  • Peer Reviewed
• [Journal Article] The effect of renal administration of a selective cyclooxygenase-2 inhibitor or stable prostaglandin I(2) analog on the progression of sclerotic glomerulonephritis in rats (2012)
  • Author(s): Nozawa Y, Sato A, Piao H, Morioka T, Narita I, Oite T
  • Journal Title: Clin Exp Nephrol Volume: 16 Pages: 221-230
  • Peer Reviewed
• [Journal Article] Weight gain after 20 years of age is associated with prevalence of chronic kidney disease (2012)
  • Author(s): Wakasugi M, Narita I, Iseki K, Moriyama T, Yamagata K, Tsuruya K, Yoshida H, Fujimoto S, Asahi K, Kurahashi I, Ohashi Y, Watanabe T
  • Journal Title: Clin Exp Nephrol Volume: 16 Pages: 259-68
  • Peer Reviewed
• [Journal Article] Injured kidney cells express SM22alpha (transgelin) : Unique features distinct from alpha-smooth muscle actin (alphaSMA) (2011)
  • Author(s): Sakamaki Y, Sakatsume M, Wang X, Inomata S, Yamamoto T, Gejyo F, Narita I
  • Journal Title: Nephrology Volume: 16 Pages: 211-8
  • Peer Reviewed
• [Journal Article] Membranoproliferative pattern of glomerular injury associated with complement component 9 deficiency due to Arg95Stop mutation (2011)
  • Author(s): Miura T, Goto S, Iguchi S, Shimada H, Ueno M, Nishi S, Narita I
  • Journal Title: Clin Eexp Nephrol Volume: 15 Pages: 86-91
  • Peer Reviewed
• [Journal Article] Megalin is downregulated via LPS-TNF-alpha-ERK1/2 signaling pathway in proximal tubule cells (2011)
  • Author(s): Takeyama A, Sato H, Soma-Nagae T, Kabasawa H, Suzuki A, Yamamoto-Kabasawa K, Hosojima M, Kaneko R, Higuchi F, Kaseda R, Ogasawara S, Narita I, Saito A
  • Journal Title: Biochem Biophys Res Com Volume: 407 Pages: 108-12
  • Peer Reviewed
• [Journal Article] Novel expression of claudin-5 in glomerular podocytes (2011)
  • Author(s): Koda R, Zhao L, Yaoita E, Yoshida Y, Tsukita S, Tamura A, Nameta M, Zhang Y, Fujinaka H, Magdeldin S, Xu B, Narita I, Yamamoto T
  • Journal Title: Cell Tissue Res Volume: 343 Pages: 637-48
  • Peer Reviewed
• [Journal Article] Nuclear chromatin-concentrated osteoblasts in renal bone diseases (2011)
  • Author(s): Kazama JJ, Yamamoto S, Narita I, Kurihara S
  • Journal Title: Ther Apher Dial Volume: 15 Suppl 1 Pages: 9-13
  • Peer Reviewed
• [Journal Article] Earthquake in Japan (2011)
  • Author(s): Kazama JJ, Narita I
  • Journal Title: Lancet Volume: 377 Pages: 1652-3
  • Peer Reviewed
• [Journal Article] The case of BK virus infection in which it was difficult to differentiate from acute rejection (2011)
  • Author(s): Ito Y, Nishi S, Imai N, Yoshita K, Saito K, Nakagawa Y, Takahashi K, Narita I
  • Journal Title: Clin Transpl Volume: 25 Suppl 23 Pages: 44-8
  • Peer Reviewed
• [Journal Article] Expression of SM22alpha (transgelin) in glomerular and interstitial renal injury (2011)
  • Author(s): Inomata S, Sakatsume M, Sakamaki Y, Wang X, Goto S, Yamamoto T, Gejyo F, Narita I
  • Journal Title: Nephron Exp Nephrol Volume: 117 Pages: e104-13
  • Peer Reviewed
• [Journal Article] Identification of alternatively activated macrophages in new-onset paediatric and adult immunoglobulin A nephropathy : potential role in mesangial matrix expansion (2011)
  • Author(s): Ikezumi Y, Suzuki T, Karasawa T, Hasegawa H, Yamada T, Imai N, Narita I, Kawachi H, Polkinghorne KR, Nikolic-Paterson DJ, Uchiyama M
  • Journal Title: Histopathology Volume: 58 Pages: 198-210
  • Peer Reviewed
• [Journal Article] Thrombotic thrombocytopenic purpura in IgG4-related disease with severe deficiency of ADAMTS-13 activity and IgG4 autoantibody against ADAMTS-13 (2011)
  • Author(s): Saeki T, Ito T, Youkou A, Ishiguro H, Sato N, Yamazaki H, Koike T, Kourakata H, Ferrari S, Scheiflinger F, Narita I
  • Journal Title: Arthritis Care Res Volume: 63 Pages: 1209-12
  • Peer Reviewed
• [Presentation] p.E66Q Variant of α-Galactosidase A Does Not Affect the Progression of Chronic Kidney Disease (2013)
  • Author(s): Watanabe H, Goto S, Maruyama H, Narita I
  • Organizer: American Society of Nephrology Kidney Week 2013
  • Place of Presentation: Atlanta, USA
  • Year and Date: 20131105-10
• [Presentation] Megalin-Mediated Mechanism of High Fat Diet-Induced Kidney Disease (2013)
  • Author(s): Hosojima M, Kuwahara S, Kabasawa H, Aoki H, Kaneko R, Narita I, Saito A
  • Organizer: American Society of Nephrology Kidney Week 2013
  • Place of Presentation: Atlanta, USA
  • Year and Date: 20131105-10
• [Presentation] Exome Sequencing Identifies a Novel EEA1 Variant in Japanese Familial IgA Nephropathy (2012)
  • Author(s): Goto S, Hosomichi K, Tsukaguchi H, Narita I
  • Organizer: American Society of Nephrology Kidney Week 2012
  • Place of Presentation: San Diego, USA
  • Year and Date: 20121030-1104
• [Presentation] Irbesartan decreases serum and urinary MCP-l levels in patients with metablolic svndrome-related nephrology (2012)
  • Author(s): Hosojima M. Kabasawa H, Suzuki Y, Narita I, Saito A
  • Organizer: ISN FOREFRONTS 2012
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 20121004-07
• [Presentation] A methodology for evaluating local care and preventing the progression of CKD (2012)
  • Author(s): Wakasugi W, Kazama JJ, Narita I
  • Organizer: The 1st Chronic Kidney Disease Frontier in Nagoya
  • Place of Presentation: Japan
  • Year and Date: 2012-02-18
• [Presentation] Genome-wide linkage scan of Japanese families with IgA nephropathy (2011)
  • Author(s): Goto S, Tsukaguchi H, Wada M, Narita I
  • Organizer: American Society of Nephrology Kidney Week 2011
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 20111108-13
• [Presentation] Prolactin receptor was up-regulated in the proximal tubules of the kidney in the cardio-renal syndrome model mice (2011)
  • Author(s): Tsuchida Y, Kaneko Y, Saito A, Yamamoto T, Narita I
  • Organizer: American Society of Nephrology Kidney Week 2011
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 20111108-13
• [Book] 次世代シークエンサー、Annual Review腎臓2013 (富野康日己、柏原直樹、成田一衛編) (2013)
  • Author(s): 後藤 眞、細道一善、成田一衛
  • Total Pages: 95-100
  • Publisher: 中外医学社
• [Book] 糖鎖不全IgAに対する新規受容体とIgA腎症発症機序 Annual Review 腎臓2012(富野康日己、柏原直樹、成田一衛編) (2012)
  • Author(s): 金子佳賢、成田一衛
  • Total Pages: 36-42
  • Publisher: 中外医学社
• [Book] 尿細管性アシドーシスとその他の尿細管疾患 今日の治療指針2011(山口 徹、北原 光夫、福井 次矢編) (2011)
  • Author(s): 成田一衛
  • Total Pages: 543-545
  • Publisher: 医学書院
• [Book] GWAS Annual Review腎臓2011(富野康日己、柏原直樹、成田一衛編) (2011)
  • Author(s): 後藤眞、成田一衛
  • Total Pages: 176-182
  • Publisher: 中外医学社
• [Book] IgA腎症の発症・進展メカニズム-エビデンスに基づいた診断と治療, IgA腎症診療マニュアル改訂第3版 (富野康日己編) (2011)
  • Author(s): 後藤眞、成田一衛
  • Total Pages: 18-24
  • Publisher: 南江堂