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Genetic dissection of familial intracranial aneurysms by family-based approach

Research Project

Project/Area Number 14207016
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionKyoto University

Principal Investigator

KOIZUMI Akio  Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (50124574)

Co-Investigator(Kenkyū-buntansha) HASHIMOTO Nobuo  Kyoto University, Professor, 医学研究科, 教授 (40135570)
MATSUDA Masayuki  Shiga University of Medical Science, Professor, 医学部, 教授 (80026947)
SUZUKI Michiyasu  Yamaguchi University, School of Medicine, Professor, 医学部, 教授 (80196873)
YOSHINAGA Takeo  Kyoto University, Associate professor, 医学研究科, 助教授 (30025663)
NOZAKI Kazuhiko  Kyoto University, Associate professor, 医学研究科, 助教授 (90252452)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥45,370,000 (Direct Cost: ¥34,900,000、Indirect Cost: ¥10,470,000)
Fiscal Year 2004: ¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000)
Fiscal Year 2003: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2002: ¥23,140,000 (Direct Cost: ¥17,800,000、Indirect Cost: ¥5,340,000)
KeywordsIntracranial aneurysm / Genome-wide analysis / Genetic susceptibility / Linkage analysis / Association study / Chromosome 17 / Family-based study / くも膜下出血 / 家系 / 遺伝子 / ApoE / 家族性 / 遺伝子解析 / 多発家族 / MRI / SNPs / リスク要因
Research Abstract

In the study from 2002 to 2004, we have investigated 5 projects. First, we had recruited a study cohort of patients with familial histories of intracranial aneurysms (IA). Second, we conducted linkage analysis in these pedigrees. Third, we recruited cases and controls for the association study. Fourth, we conducted a replicating study for genes reported to be associated with IAs. Finally, we have tested whether a candidate gene found in pedigree study is associated with IA by a case-control study.
1. A study cohort of pedigrees with familial IA : 29 families were recruited. From these families, 169 members took MRA screening. In these families, 104 members were found to have IA. Totally 273 members joined this study.
2. Linkage analysis : We have conducted a linkage analysis for 29 families. The result revealed three significant regions : 17cent,19q13,and Xp22.
3. A population for case-control study. Cases were defined as those who have been found to have IA by MRA/MRI or 3DCT angiography or angiography or been found to have IA by surgery for SAH. Controls were defined as those who were not having IA by MRA/MRI, are older than 40 years and are without family histories or histories of cerebrovascular diseases. Finally, we recruited 362 members and 332 members for cases and controls, respectively.
4. A replication study : We have tested whether genes previously reported could be replicated or not. We selected Elastin (7q11), NOS2A(17cent), APOE (19q13) and ACE2(Xp22). We failed to replicate none of these genes in our population.
5. Genes on 17cent : There are 108 genes on the linked region of chromosome 17cent. We selected 9 genes (TNFRSF13,M-RIP, COPS3,RAI1,SREBF1,GRAP MAPK7,MFPK7 and AKAP10) from this region. We conducted family study and case control studies'. A significant linkage and association was confirmed for TNFRSF13B.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (48 results)

All 2006 2005 2004 2003 2002 Other

All Journal Article (29 results) Book (8 results) Publications (11 results)

  • [Journal Article] Association Analysis of Common Variants of ELN, NOS2A, APOE and ACE2 to Intracranial Aneurysm2006

    • Author(s)
      Mineharu Y. et al.
    • Journal Title

      Stroke 37

      Pages: 1189-1194

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Search on Chromosome 17 Centromere Reveals TNFRSF13B as a Susceptibility Gene for Intracranial Aneurysm A Preliminary Study2006

    • Author(s)
      Inoue K. et al.
    • Journal Title

      Circulation 113

      Pages: 2002-2010

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Nonsense Polymorphism of SLC6A18 (Solute Carrier Family 6 Member 18) does not contribute to hypertension and blood pressure in humans2006

    • Author(s)
      Eslami B. et al.
    • Journal Title

      Tohoku J Exp Med 208

      Pages: 25-31

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A PTPNII gene mutation (Y63C) causing Noonan syndrome is not associated with short stature in general population2006

    • Author(s)
      Takahashi I. et al.
    • Journal Title

      Tohoku J Exp Med 208

      Pages: 255-259

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association Analysis of Common Variants of ELN NOS2A, APOE and ACE2 to Intracranial Aneurysm2006

    • Author(s)
      Mineharu Y. et al.
    • Journal Title

      Stroke 37

      Pages: 1189-1194

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Search on Chromosome 17 Centromere Reveals TNFRSFJ3B as a Susceptibility Gene for Intracranial Aneurysm A Preliminary Study2006

    • Author(s)
      Inoue K. et al.
    • Journal Title

      Circulation 113

      Pages: 2002-2010

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Nonsense Polymorphism of SLC6A18 (Solute Carrier Family 6 Member 18) does not contribute to hypertension and blood pressure in humans2006

    • Author(s)
      Eslami B et al.
    • Journal Title

      Tohoku J Exp Med 208

      Pages: 25-31

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A PTPN11 gene mutation (Y63C) causing Noonan syndrome is not associated with short stature in general population2006

    • Author(s)
      Takahashi I et al.
    • Journal Title

      Tohoku J Exp Med 208

      Pages: 255-259

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Long-acting gonadotropin-releasing hormone analogue treatment for central precocious puberty in maternal uniparental disomy chromosome 142005

    • Author(s)
      Takahashi I. et al.
    • Journal Title

      Tohoku J Exp Med 207

      Pages: 333-338

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] History of blood transfusion before 1990 is a risk factor for stroke and cardiovascular biseases : the Japan collaborative cohort study (JACC study)2005

    • Author(s)
      Yamada S. et al.
    • Journal Title

      Cerebrovase Dis 20(3)

      Pages: 164-71

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Long-acting gonadotropin-releasing hormone analogue treatment for central precocious puberty in maternal uniparental disomy chromosome 142005

    • Author(s)
      Takahashi I et al.
    • Journal Title

      Tohoku J Exp Med 207

      Pages: 333-338

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] History of blood transfusion before 1990 is a risk factor for stroke and cardiovascular diseases : the Japan collaborative cohort study (JACC study)2005

    • Author(s)
      Yamada S. et al.
    • Journal Title

      Cerebrovasc Dis 20(3)

      Pages: 164-171

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Genome-Wide Scan for Japanese Familial Intracranial Aneurysms : Linkage to Several 'Chromosomal Regions2004

    • Author(s)
      Yamada S. et al.
    • Journal Title

      Circulation 110

      Pages: 3727-3733

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mutations in SLC6A19 (hBOAT1) are Associated with Hartnup disorder2004

    • Author(s)
      Kleta R. et al.
    • Journal Title

      Nat Genet 36

      Pages: 999-1002

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 脳神経外科疾患の責任遺伝子解析の概説2004

    • Author(s)
      小泉昭夫 外
    • Journal Title

      脳神経外科 32

      Pages: 1203-1213

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Genome-Wide Scan for Japanese Familial Intracranial Aneurysms : Linkage to Several Chromosomal Regions2004

    • Author(s)
      Yamada S. et al.
    • Journal Title

      Circulation 110

      Pages: 3727-3733

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mutations in SLC6A19 (hBOAT1) are Associated with Hartnup disorder2004

    • Author(s)
      Kleta R. et al.
    • Journal Title

      Net Genet 36

      Pages: 999-1002

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] An Overview of Genetic Analysis for Neurosurgical Diseases and Disorders2004

    • Author(s)
      Koizumi A. et al.
    • Journal Title

      Neurological surgery 32

      Pages: 1203-1213

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Genome-Wide Scan for Japanese Familial Intracranial Aneurysms2004

    • Author(s)
      Yamada et al.
    • Journal Title

      Circulation 110

      Pages: 3727-3733

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 脳神経外科疾患の責任遺伝子解析の概説2004

    • Author(s)
      小泉 昭夫 外
    • Journal Title

      脳神経外科 32

      Pages: 1203-1213

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 家族性脳動脈奇形の遺伝子解析2004

    • Author(s)
      竹中 勝信 外
    • Journal Title

      脳神経外科ジャーナル別冊 13

      Pages: 837-845

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Absence of Linkage of Familial Intracranial Aneurysms to 7q11 in Highly Aggregated Japanese Families2003

    • Author(s)
      Yamada S. et al.
    • Journal Title

      Stroke 34

      Pages: 892-900

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Risk factors for fatal subarachnoid hemorrhage : The Japan Collaborative Cohort study2003

    • Author(s)
      Yamada S. et al.
    • Journal Title

      Stroke 34

      Pages: 2781-2787

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A historical aspect of Lysinuric protein intolerance in a northern part of Iwate, Japan2003

    • Author(s)
      Inoue Y. et al.
    • Journal Title

      Human Biol 75

      Pages: 81-90

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Evaluation of a Mass Screening Program for Lysinuric Protein Intolerance in the Northern Part of Japan2003

    • Author(s)
      Koizumi A. et al.
    • Journal Title

      Genetic Testing 7

      Pages: 29-35

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Risk factors for fatal subarachnoid hemorrhage2003

    • Author(s)
      Yamada S. et al.
    • Journal Title

      Stroke 34

      Pages: 2781-2787

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mutation Analysis in PKD1 of Japanese Autosomal Dominant Polycystic Kidney Disease Patients2002

    • Author(s)
      Inoue S. et al.
    • Journal Title

      Human Mutation 19

      Pages: 622-628

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Genetic epidemiology of hereditary homorrhagic telagioectasia in a local community in the northern part of Japan2002

    • Author(s)
      Dakeishi M. et al.
    • Journal Title

      Human Mutation 19

      Pages: 140-148

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Genetic epidemiology of hereditary hemorrhagic telagioectasia in a local community in the northern part of Japan2002

    • Author(s)
      Dakeishi M. et al.
    • Journal Title

      Human Mutation 19

      Pages: 140-148

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 家族性能動脈瘤 日本臨床 : 2006年 増刊 インターベンション時代の脳卒中学(下) -超急性期から再発予防まで-2006

    • Author(s)
      山田茂樹 外
    • Publisher
      日本臨牀社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 総論 分子疫学/EBM 分子予防環境医学-分子予防環境医学研究会2003

    • Author(s)
      宇都宮真木 外
    • Total Pages
      768
    • Publisher
      本の泉社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 各論IV ゲノム医科学の分子予防医学への統合 遺伝情報管理システム 子予防環境医学-分子予防環境医学研究会編2003

    • Author(s)
      井上悠輔 外
    • Total Pages
      768
    • Publisher
      本の泉社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 病気の原因遺伝子単離のための戦略、疾患とフィールドの選択 これだけは知っておきたい遺伝子医学の基礎知識2003

    • Author(s)
      井上悠輔 外
    • Total Pages
      309
    • Publisher
      メディカル ドゥ
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] The general remarks Molecular epidemiology Integration of modern life science into preventive and environmental medicine2003

    • Author(s)
      Utsunomiya M. et al.
    • Total Pages
      768
    • Publisher
      Honnoizumisya
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Detailed exposition IV-3 Management of genetic database Integration of modern life science into preventive and environmental medicine2003

    • Author(s)
      Inoue Y. et al.
    • Total Pages
      768
    • Publisher
      Honnoizumisya
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Strategy of genetic analysis Basic Genetics in Medicine2003

    • Author(s)
      Inoue Y. et al.
    • Total Pages
      309
    • Publisher
      Medical Do
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Stroke in Intervention era Familial intracranial aneurysm

    • Author(s)
      Yamada S. et al.
    • Publisher
      Nihon Rinshosya
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Yamada S, et al.: "Absence of linkage of familial intracranial aneurysms to 7q.11 in highly aggregated Japanese Families"Stroke. 34. 892-900 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sadamasa N, et al.: "Disruption of gene for inducible nitric oxide synthase reduces progression of cerebral aneurysms"Stroke. 34. 2980-2984 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamada S, et al.: "Jacc Srydy group Risk factors for fatal subarchnoid hemorrhage : The Japana Collaborative Cohort study"Stroke. 34. 2781-2787 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nozaki J, et al.: "Point mutation of isulin Cystein 96 stimulate endoplasmic reticulum stress response through …"Genes to Cells. In press. (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamada S, et al.: "A Genome-Wide Scan for Japanese Familial Intracranial Aneurysms : Evidence for Linkages to Several Chromosomal Regions"Circulation. In press. (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Dakeishi et al.: "Genetic epidemiology of hereditary hemorrhagic telagioectasia in a localcommunity in the northern part of Japan"Human mutation. 19. 140-148 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Inoue et al.: "Mutation Analysis of PKD1 in Japanese Autosomal Dominant Polycystic Kidney Disease (ADPKD)Patients"Human mutation. 19. 622-628 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iso et al.: "Perceived Mental Stress and Mortality From Cardiovascular Disease Among Japanese Men and Women"Circulation. 106. 1229-1236 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shoji et al.: "Five novel SLC7A7 variants and y+L gene-expression pattern in cultured lymphoblasts from Japanese patients with lysinuric protein intolerance"Human mutation. 20. 375-381 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Koizumi et al.: "Evaluation of a Mass Screening Program for Lysinuric Protein Intolerance in the Northern Part of Japan"Genetic Testing. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamada et al.: "Absence of Linkage of Familial Intracranial Aneurysms to 7q11 in Highly Aggregated Japanese Families"Stroke. (in press). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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