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Identification of susceptible genes for essential hypertension

Research Project

Project/Area Number 12203001
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionGraduate School of Medicine, Chiba university (2002-2004)
Asahikawa Medical College (2000-2001)

Principal Investigator

HATA Akira  Chiba University, Graduate School of Medicine, Professor, 大学院医学研究院, 教授 (00244541)

Co-Investigator(Kenkyū-buntansha) KIKUCHI Kenjiro  Asahikawa Medical College, Professor, 医学部, 教授 (30045455)
INOUE Ituro  The University of Tokyo, The Institute of Medical Science, Associate Professor, 医科学研究所, 客員助教授 (00192500)
MAKITA Yoshio  Asahikawa Medical College, Assistant Professor, 医学部, 助手 (20271778)
SUGIYAMA Takuro  Asahi life Foundation, The Institute of common diseases of adulthood, Laboratory Head, 検査部, 部長
SHIWAKU Kiminori  Shimane University, Faculty of Medicine, 医学部, 助教授 (10108384)
江藤 胤尚  宮崎医科大学, 医学部, 教授 (10038854)
島本 和明  札幌医科大学, 医学部, 教授 (40136940)
川村 実  岩手医科大学, 医学部, 助教授 (30142178)
藤田 敏郎  東京大学, 医学部, 教授 (10114125)
Project Period (FY) 2000 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥107,800,000 (Direct Cost: ¥107,800,000)
Fiscal Year 2004: ¥25,000,000 (Direct Cost: ¥25,000,000)
Fiscal Year 2003: ¥26,400,000 (Direct Cost: ¥26,400,000)
Fiscal Year 2002: ¥26,400,000 (Direct Cost: ¥26,400,000)
Fiscal Year 2001: ¥30,000,000 (Direct Cost: ¥30,000,000)
Keywordsessential hypertension / susceptible genes / haplotype / haplotype association study / SNPs / ハプロタイプ / 関連解析 / LDブロック / 発症関連遺伝子 / ゲノムワイド / 本能性高血圧 / DOP-PCR / ガイドライン / 連鎖不平衡
Research Abstract

To identify susceptible genes for essential hypertension, following four steps were conducted. 1. sample collection from all over Japan, 2. selection of candidate genes, 3. haplotype construction of the candidate genes, 4. haplotype association study of candidate genes.
For sample collection, clinical cardiologists, epidemiologists, doctors working on regional health check-up were recruited from all over Japan. Thanks to them, a total of 1600 samples from clinics and 2200 samples from epidemiological population in the region have been obtained. Of these samples, a total of 200 cases and 200 controls were extracted to initial genotyping. Candidate genes were selected from two sources. One was derived from the human homologue genes that significantly increased or decreased expression in the mouse kidneys after more than three months of high salt diet detected by way of microarray analysis. The other was extracted from the reported genes in literature that expressed mainly in human kidney. A total of 121genes were assigned for candidates. Haplotype was successfully constructed in 73 genes with SNPs from Japanese SNP database (J-SNP). Then SNPs of the 73 genes were genotyped with 888 hypertensive cases and 840 normotensive controls (samples from Ehime, Osaka and Nippon Universities were added to ours). Both contingency table method and haplotype inference method were employed to haplotype association study. Finally ten genes have been survived through the screening steps. Of these, three candidate genes have been analyzed now.

Report

(6 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (37 results)

All 2004 2003 2002 2001 Other

All Journal Article (15 results) Publications (22 results)

  • [Journal Article] A1166C variant of angiotensinogen II type 1 receptor gene is associated with severe hypertension in pregnancy independently of T235 variant of angiotensinogen gene.2004

    • Author(s)
      Kobashi G et al.
    • Journal Title

      J Hum Genet 49

      Pages: 182-189

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A1166C variant of angiotensinogen II type 1 receptor gene is associated with severe hypertension in pregnancy independently of T235 variant of angiotensinogen gene2004

    • Author(s)
      Kobashi G et al.
    • Journal Title

      J Hum Genet 49

      Pages: 182-186

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association analysis of SLC22A4,SLC22A5 and DLG5 in Japanese patients with Crohn disease.2004

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

      J Hum Genet 49

      Pages: 664-668

    • Related Report
      2004 Annual Research Report
  • [Journal Article] CD40 ligand gene and Kawasaki disease.2004

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

      Eur J Hum Genet 12

      Pages: 1062-1068

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A1166C variant of angiotensiogen II type I receptor gene is associated with severe hypertension in pregnancy independently of T235 variant of angiotensinogen gene.2004

    • Author(s)
      Kobashi G et al.
    • Journal Title

      J Hum Genet 49

      Pages: 182-186

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Common origin of the Val30Met mutation responsible for the amyloidogenic transthyretin type of familial amyloidotic polyneuropathy.2004

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

      J Med Genet 41

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Haplotype analysis of human collectin placenta 1 (hCH-P1) gene.2003

    • Author(s)
      Ohmori H et al.
    • Journal Title

      J Hum Genet 48

      Pages: 82-85

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association between a variant of the glutathione S-transferase P1 gene (GSTP1) and hypertension in pregnancy in Japanese : Interaction with parity, age, and genetic factors2003

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

      Semin Thromb Hemost 29

      Pages: 653-659

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Nucleotide diversity and haplotype structure of the human angiotensigen gene in two populations.2002

    • Author(s)
      Nakajima T et al.
    • Journal Title

      Am J Hum Genet 70

      Pages: 108-123

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Linkage and association analyses of the osteoprotegerin gene locus with human osteoporosis.2002

    • Author(s)
      Ohmori H et al.
    • Journal Title

      J Hum Genet 47

      Pages: 400-406

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The M235T variant of the angiotensinogen gene and the body mass index are useful markers for prevention of hypertension in pregnancy : a tree-based analysis of gene-environmental interaction.2002

    • Author(s)
      Kobashi G et al.
    • Journal Title

      Semin Thromb Hemost 28

      Pages: 501-506

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Nucleotide diversity and haplotype structure of the human angiotensigen gene in two populations.2002

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

      Am J Hum Genet 70

      Pages: 108-123

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The M235T variant of the angiotensinogen gene and the body mass index are useful markers for prevention of hypertension in pregnancy : a tree-based analysis of gene-environmental interaction2002

    • Author(s)
      Kobashi G et al.
    • Journal Title

      Semin Thromb Hemost 28

      Pages: 501-506

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Multivariate analysis of genetic and acquired factors; T235 variant of the angiotensinogen gene is a potent independent risk factor for preeclampsia.2001

    • Author(s)
      Kobashi G et al.
    • Journal Title

      Semin Thromb Hemost 27

      Pages: 143-147

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Multivariate analysis of genetic and acquired factors ; T235 variant of the angiotensinogen gene is a potent independent risk factor for preeclampsia.2001

    • Author(s)
      Kobashi G et al.
    • Journal Title

      Semin Thromb Hemost 27

      Pages: 143-147

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Ohmori H et al.: "Linkage and association analyses of the osteoprotegerin gene locus with human osteoporosis."J Hum Genet. 47. 400-406 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kobashi G et al.: "An association between maternal smoking and preeclampsia in Japanese women."Semin Thromb Hemost. 28. 507-510 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kobashi G et al.: "The M235T variant of the angiotensinogen gene and the body mass index are useful markers for prevention of hypertension in pregnancy : a tree-based analysis of gene-environmental interaction"Semin Thromb Hemost. 28. 501-506 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohmori H et al.: "Haplotype analysis of human collectin placenta 1 (hCH-P1) gene."J Hum Genet. 48. 82-85 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohmori H et al.: "Common origin of the Val30Met mutation responsible for the amyloidogenic transthyretin type of familial amyloidotic polyneuropathy."J Mod Genet. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kobashi, et al.: "A1166C variant of angiotensinogen II type 1 receptor gene is associated with severe hypertension in pregnancy independent of T235 variant of angiotensinogen gene."J Hum Genet. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakamura T et al.: "Methylenetetrahydrofolate reductase genotype, vitamine B_<12> and folate influence plasma homocysteine in hemodialysis patients."Am J Kidney Dis. 39. 1032-1039 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohmori H et al.: "Linkage and association analyses of the osteoprotegerin gene locus with human osteoporosis"J Hum Genet. 47. 400-406 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohmi H et al.: "Post-traumatic stress disorder in pre-school aged children after a gas explosion"Eur J Pediatr. 161. 643-648 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kobashi G et al.: "An association between maternal smoking and preeclampsia in Japanese women"Semin Thromb Hemost. 28. 507-510 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kobashi G et al.: "The M235T variant of the angiotensinogen gene and the body mass index are useful markers for prevention of hypertension in pregnancy : a tree-based analysis of gene-environmental interaction"Semin Thromb Hemost. 28. 501-506 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohmori H et al.: "Haplotype analysis of human collectin placenta 1 (hCH-P1) gene"J Hum Genet. 48. 82-85 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakajima T et al.: "Nucleotide diversity and haplotype structure of the human angiotensinogen gene in two populations"Am.J.Hum.Genet.. 70. 108-123 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Arima T et al.: "A conseved imprinting control region at the HYMAI/ZAC domain is implicated in transient neonatal diabetes mellitus"Hum.Mol.Genet.. 10. 1475-1484 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobashi G et al.: "Multivariate analysis of genetic and acquired factors ; T235 variant of the angiotensinogen gene is a potent ----"Semin Thromb Hemost. 27. 143-147 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohmori H et al.: "Linkage and association analyses of osteoprotegerin gene locus to human osteoporosis"Hum.Genet.. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobashi G et al.: "Absence of association between a common mutation in the methylenetetrahydrofolate reductase gene and preeclampsia in Japanese women"Am J Med Genet. 93. 122-125 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ikeda Y et al.: "Advanced glycation end products-induced gene expression of scavenger receptors in cultured human monocyte-derived macrophages"J Lab Clin Med. 135. 353-359 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohmi H et al.: "The centenary of the enactment of the law for prohibiting minors from smoking in Japan"Tobacco Control. 9. 258 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohmi H et al.: "Recent trend of increase in proportion of low birthweight infants in Japan."Int J Epidemiology. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Iwashima Y et al.: "Angiotensin II-induced cardiomyocyte hypertrophy and cardiac fibrosis in stroke-prone spontaneously hypertensive rats"Biochem Biophys Res Com. 277. 368-380 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 羽田明,大濱紘三 編: "新女性医学大系 28 遺伝の基礎と臨床"中山書店. 461 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2001-04-01   Modified: 2018-03-28  

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