• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Exploring for susceptible genes for hypertension and atherosclerosis.

Research Project

Project/Area Number 12204008
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionEhime University

Principal Investigator

MIKI Tetsuro  Ehime University School of Medicine, Department of Geriatric Medicine, Professor, 医学部, 教授 (00174003)

Co-Investigator(Kenkyū-buntansha) KOHARA Katsuhiko  Ehime University School of Medicine, Department of Geriatric Medicine, Associate Professor, 医学部, 助教授 (30260384)
NAKURA Jun  Ehime University School of Medicine, Department of Geriatric Medicine, Lecturer, 医学部附属病院, 講師 (70304607)
TABARA Yasuharu  Ehime University School of Medicine, Department of Geriatric Medicine, Assistant, 医学部, 講師 (00268749)
Project Period (FY) 2000 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥92,800,000 (Direct Cost: ¥92,800,000)
Fiscal Year 2004: ¥23,000,000 (Direct Cost: ¥23,000,000)
Fiscal Year 2003: ¥22,400,000 (Direct Cost: ¥22,400,000)
Fiscal Year 2002: ¥22,400,000 (Direct Cost: ¥22,400,000)
Fiscal Year 2001: ¥25,000,000 (Direct Cost: ¥25,000,000)
Keywordshypertension / atherosclerosis / single nucleotide polymorphism / gene-environmental interaction / 循環器疾患 / 感受性遺伝子 / SNP / ケース / コントロール / 動脈硬化関連遺伝子 / 高血圧関連遺伝子 / 多型 / オッズ比 / 95%信頼限界 / 相互作用解析 / マイクロサテライトマーカー / 遺伝子 / 相互作用 / ゲノムワイドスキャニング / SNPs
Research Abstract

In the present study, we explored susceptible genes for the development of hypertension and atherosclerosis by the genome-wide systemic candidate gene screening. A susceptibility of the already-known candidate genes was also re-evaluated. The genome-wide screening was carried out using 1,400 hypertensive/normotensive subjects. The validity of screened genes, as well as already-known candidate genes, was assessed using 11,000 community-based Japanese subjects colleted from the nation-wide. To explore the susceptibility of genes for multi-factorial disease, a gene-environmental interaction was considered in the analysis.
1. large-scale genetic epidemiological study cohort
In addition to the own recruitment, the study subjects were collected from the nation-wide in collaboration with other investigators. A total number of 11,000 subjects having detailed clinical information were finally collected.
2. case-control subjects
Approximately 1400 of hypertensive and normotensive subjects (700 subje … More cts each) were collected from the nation-wide for the purpose of screening of candidate genes.
3. high-throughput genotyping system
A high-throughput genotyping system which can determine more than 12,000 genotypes per day was constructed.
4. genome-wide candidate gene screening
A susceptibility of approximately 300 SNPs locating in genes encoding the components of signal transduction system were evaluated using the case/control subjects, and the 38 SNPs showed statistically significant. Validity of these positive SNPs was evaluated using the large-scale Japanese subjects.
5. gene-environmental interaction
The already-known candidate genes for hypertension were re-analyzed by the view of gene-environmental interaction. Although marked direct association was not observed in any gene, several genes showed significant association with the interaction with other environmental factors.
The accumulation of these evidences contributes to clarify the genetic background of hypertension and atherosclerosis. Less

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

    (53 results)

All 2005 2004 2003 2002 2001 2000 Other

All Journal Article (29 results) Patent(Industrial Property Rights) (1 results) Publications (23 results)

  • [Journal Article] 17-year follow-up study of a patient with obstructive hypertrophic cardiomyopathy with a deletion mutation in the cardiac myosin binding protein C gene.2004

    • Author(s)
      Ogimoto A
    • Journal Title

      Circ J 68

      Pages: 174-177

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 17-year follow-up study of a patient with obstructive hypertrophic cardiomyopathy with a deletion mutation in the cardiac myosin binding protein C gene.2004

    • Author(s)
      Ogimoto A, Hamada M, Nakura J, Shigematsu Y, Hara Y, Ohtsuka T, Morishima A, Kimura A, Miki T, Hiwada K.
    • Journal Title

      Circ J. 68

      Pages: 174-7

    • NAID

      110002667503

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association of GNB3 gene with pulse pressure and clustering of risk factors for cardiovascular disease in Japanese.2004

    • Author(s)
      Yamamoto M, Abe M, Jin JJ, Wu Z, Tabara Y, Mogi M, Kohara K, Miki T, Nakura J.
    • Journal Title

      Biochem Biophys Res Commun 316(3)

      Pages: 744-748

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effect of genetic polymorphism of OATP-C (SLCO1B1) on lipid-lowering response to HMG-CoA reductase inhibitors.2004

    • Author(s)
      Tachibana-Iimori R, Tabara Y, Kusuhara H, Kohara K, Kawamoto R, Nakura J, Tokunaga K, Kondo I, Sugiyama Y, Miki T.
    • Journal Title

      Drug Metab Pharmacokinet. 19(5)

      Pages: 375-380

    • NAID

      10014314699

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Genetic predisposition to neurological symptoms in lacunar infarction.2004

    • Author(s)
      Zhang JH, Kohara K, Yamamoto Y, Nakura J, Tabara Y, Fujisawa M, Katagi R, Miki T
    • Journal Title

      Cerebrovasc Dis 17(4)

      Pages: 273-279

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Association of endothelin-1 gene variant with hypertension.2003

    • Author(s)
      Jin JJ
    • Journal Title

      Hypertension. 41

      Pages: 163-167

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association of angiotensin II type 2 receptor gene variant with hypertension.2003

    • Author(s)
      Jin JJ
    • Journal Title

      Hypertens Res. 26

      Pages: 547-552

    • 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 linkage disequilibrium mapping of hypertension in Japan.2003

    • Author(s)
      Wu Z
    • Journal Title

      Hypertens Res. 26

      Pages: 533-540

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association of I27L polymorphism of hepatocyte nuclear factor-l alpha gene with high-density lipoprotein cholesterol level.2003

    • Author(s)
      Babaya N
    • Journal Title

      J Clin Endocrinol Metab. 88

      Pages: 2548-2551

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association of endothelin-l gene variant with hypertension.2003

    • Author(s)
      Jin JJ, Nakura J, Wu Z, Yamamoto M, Abe M, Tabara Y, Yamamoto Y, Igase M, Kohara K, Miki T.
    • Journal Title

      Hypertension. 41

      Pages: 163-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association of angiotensin II type 2 receptor gene variant with hypertension.2003

    • Author(s)
      Jin JJ, Nakura J, Wu Z, Yamamoto M, Abe M, Chen Y, Tabara Y, Yamamoto Y, Igase M, Bo X, Kohara K, Miki T.
    • Journal Title

      Hypertens Res. 26

      Pages: 547-52

    • NAID

      10011242106

    • 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 linkage disequilibrium mapping of hypertension in Japan.2003

    • Author(s)
      Wu Z, Nakura J, Abe M, Jin JJ, Yamamoto M, Chen Y, Tabara Y, Yamamoto Y, Igase M, Bo X, Kohara K, Miki T.
    • Journal Title

      Hypertens Res. 26

      Pages: 533-40

    • NAID

      50000877267

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association of I27L polymorphism of hepatocyte nuclear factor-1 alpha gene with high-density lipoprotein cholesterol level.2003

    • Author(s)
      Babaya N, Ikegami H, Fujisawa T, Nojima K, Itoi-Babaya M, Inoue K, Nakura J, Abe M, Yamamoto M, Jin JJ, Wu Z, Miki T, Fukuda M, Ogihara T.
    • Journal Title

      J Clin Endocrinol Metab. 88

      Pages: 2548-51

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Genotype-specific association between circulating soluble cellular adhesion molecules and carotid intima-media thickness in community residents :2002

    • Author(s)
      Kohara K
    • Journal Title

      Hypertens Res. 25

      Pages: 31-39

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association of GNAS1 gene variant with hypertension depending on smoking status.2002

    • Author(s)
      Abe M
    • Journal Title

      Hypertension. 40

      Pages: 261-265

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Polymorphisms of genes encoding components of the sympathetic nervous system but not the renin-angiotensin system as risk factors for orthostatic hypotension.2002

    • Author(s)
      Tabara Y
    • Journal Title

      J Hypertens. 20

      Pages: 651-656

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Gene for medical cost?2002

    • Author(s)
      Tabara Y
    • Journal Title

      J Am Geriatr Soc. 50

      Pages: 775-776

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] An interaction between systolic blood pressure and angiotensin-converting enzyme gene polymorphism on carotid atherosclerosis.2002

    • Author(s)
      Kawamoto R
    • Journal Title

      Hypertens Res. 25

      Pages: 875-880

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Genotype-specific association between circulating soluble cellular adhesion molecules-and-carotid intima-media thickness in community-residents : J-SHIPP study. Shimanami Health Promoting Program.2002

    • Author(s)
      Kohara K, Tabara Y, Yamamoto Y, Igase M, Nakura J, Miki T.
    • Journal Title

      Hypertens Res. 25

      Pages: 31-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association of GNAS1 gene variant with hypertension depending on smoking status.2002

    • Author(s)
      Abe M, Nakura J, Yamamoto M, Jin JJ, Wu Z, Tabara Y, Yamamoto Y, Igase M, Kohara K, Miki T.
    • Journal Title

      Hypertension. 40

      Pages: 261-5

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Polymorphisms of genes encoding components of the sympathetic nervous system but not the renin-angiotensin system as risk factors for orthostatic hypotension.2002

    • Author(s)
      Tabara Y, Kohara K, Miki T.
    • Journal Title

      J Hypertens. 20

      Pages: 651-6

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Gene for medical cost?2002

    • Author(s)
      Tabara Y, Kohara K, Ohnishi M, Nakura J, Miki T.
    • Journal Title

      J Am Geriatr Soc. 50

      Pages: 775-6

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] An interaction between systolic blood pressure and angiotensin-converting enzyme gene polymorphism on carotid atherosclerosis.2002

    • Author(s)
      Kawamoto R, Kohara K, Tabara Y, Miki T.
    • Journal Title

      Hypertens Res. 25

      Pages: 875-80

    • NAID

      10010315267

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Risk factor-gene interaction in carotid atherosclerosis : effect of gene polymorphisms of renin-angiotensin system.2001

    • Author(s)
      Tabara Y
    • Journal Title

      J Hum Genet. 46

      Pages: 278-284

    • NAID

      10011572317

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] An association of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and common carotid atherosclerosis.2001

    • Author(s)
      Kawamoto R
    • Journal Title

      J Hum Genet 46

      Pages: 506-510

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Risk factor-gene interaction in carotid atherosclerosis : effect of gene polymorphisms of renin-angiotensin system.2001

    • Author(s)
      Tabara Y, Kohara K, Nakura J, Miki T.
    • Journal Title

      J Hum Genet. 46

      Pages: 278-84

    • NAID

      10011572317

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] An association of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and common carotid atherosclerosis.2001

    • Author(s)
      Kawamoto R, Kohara K, Tabara Y, Miki T, Doi T, Tokunaga H, Konishi I.
    • Journal Title

      J Hum Genet. 46

      Pages: 506-10

    • NAID

      10011573136

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Deletion polymorphism of ACE gene is associated with higher blood pressure after hospitalization in normotensive subjects.2000

    • Author(s)
      Uemura K
    • Journal Title

      Hypertens Res. 23

      Pages: 201-205

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Deletion polymorphism of ACE gene is associated with higher blood pressure after hospitalization in normotensive subjects.2000

    • Author(s)
      Uemura K, Kohara K, Nakura J, Miki T.
    • Journal Title

      Hypertens Res. 23

      Pages: 201-205

    • NAID

      10008739228

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 高血圧の遺伝子マーカー2005

    • Inventor(s)
      三木哲郎 他14名
    • Industrial Property Rights Holder
      愛媛大学 他5大学
    • Industrial Property Number
      2005-344267
    • Filing Date
      2005-11-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Yamamoto M, Abe M, Jin JJ, Wu Z, Tabara Y, Mogi M, Kohara K, Miki T, Nakura J.: "Association of GNB3 gene with pulse pressure and clustering of risk factors for cardiovascular disease in Japanese."Biochem Biophys Res Commun. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tabara Y, Kohara K, Yamamoto Y, Igase M, Nakura J, Kondo I, Miki T.: "Polymorphism of the monocyte chemoattractant protein (MCP-1) gene is associated with the plasma level of MCP-1 but not with carotid intima-media thickness."Hypertens Res. 26・9. 677-683 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Jin JJ, Nakura J, Wu Z, Yamamoto M, Abe M, Chen Y, Tabara Y, Yamamoto Y, Igase M, Bo X, Kohara K, Miki T.: "Association of angiotensin II type 2 receptor gene variant with hypertension."Hypertens Res. 26・7. 547-552 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Wu Z, Nakura J, Abe M, Jin JJ, Yamamoto M.Chen Y.Tabara Y, Yamamoto Y, Igase M, Bo X, Kohara K, Miki T.: "Genome-wide linkage disequilibrium mapping of hypertension in Japan."Hypertens Res. 26・7. 533-540 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Chen Y, Nakura J, Jin JJ, Wu Z, Yamamoto M, Abe M, Tabara Y, Yamamoto Y, Igase M, Bo X, Kohara K, Miki T.: "Association of the GNASI gene variant with hypertension is dependent on alcohol consumption."Hypertens Res. 26・6. 439-444 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kohara K, Tabara Y, Yamamoto Y, Igase M, Nakura J, Miki T: "Genotype-specific association between circulating soluble cellular adhesion molecules and carotid intima-media thickness in community residents : J-SHIPP study. Shimanami Health Promoting Program"Hypertens Res.. 25. 31-39 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tabara Y, Kohara K, Ohnishi M, Nakura J, Miki T: "Gene for medical cost?"J Am Geriatr Soc.. 50. 775-776 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Abe M, Nakura J, Yamamoto M, Jin JJ, Wu Z, Tabara Y, Yamamoto Y, Igase M, Kohara K, Miki T: "Association of GNAS1 gene variant with hypertension depending on smoking status"Hypertension. 40. 261-265 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsubara-Tsutsui M, Yamagata H, Morishima A, Nakura J, Mitsuda N, Kamino K, Kondo I, Miki T: "The 4, 752 C/T polymorphism in the presenilin 1 gene increases the risk of Alzheimer's disease in apolipoprotein E4 carriers"Intern Med.. 41. 823-828 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamamoto Y, Kohara K, Tabara Y, Igase M, Nakura J, Miki T: "Plasma hepatocyte growth factor and the relationship between risk factors and carotid atherosclerosis"Hypertens Res.. 25. 661-667 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Jin JJ, Nakura J, Wu Z, Yamamoto M, Abe M, Tabara Y, Yamamoto Y, Igase M, Kohara K, Miki T: "Association of endothelin-1 gene variant with hypertension"Hypertension. 41. 163-167 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Chen Y, Nakura J, Jin JJ, Wu Z, Yamamoto M, Abe M, Tabara Y, Yamamoto Y, Igase M, Bo X, Kohara K, Miki T: "Association of the GNAS1 gene variant with hypertension is dependent on alcohol consumption"Hypertens Res.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Wu Z, Nakura J, Abe M, Jin JJ, Yamamoto M, Chen Y, Tabara Y, Yamamoto Y, Igase M, Bo X, Kohara K, Miki T: "Genome-wide linkage disequilibrium mapping of hypertension in Japan"Hypertens Res.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] JiJJ: "Initial step towards identification of hypertension-related genes : Genome-wide linkage disequilibrium mapping of hypertension in Japanese"Atherosclerosis. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto Y: "Association between carotid arterial remodeling and plasma concentration of circulating hepatocyte growth factor"J Hypertens. 19・11. 1975-1979 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawamoto R: "An association of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and common carotid atherosclerosis"J Hum Genet. 46・9. 506-510 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsubara M: "Genetic association between Alzheimer disease and the alpha-synuclein gene"Dement Geriatr Cogn Disord. 12・2. 106-109 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tabara Y: "Risk factor-gene interaction in carotid atherosclerosis : effect of gene polymorphisms of renin-angiotensin system"J Hum Genet. 46・5. 278-284 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kayahara H: "Frequent loss of heterozygosity at 3p25-p26 is associated with invasive oral squamous cell carcinoma"J Hum Genet. 46・6. 335-341 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Uemura K,Kohara K,Nakura J and Miki T: "Deletion polymorphism of ACE gene is associated with higher blood pressure after hospitalization in normotensive subjects."Hypertens Res. 23. 201-205 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Uemura K.,Nakura J.,Kohara K.and Miki T: "Association of ACE I/D polymorphism with cardiovascular risk factors."Hum Genet. 107. 239-242 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kohara K,Tabara Y,Yamamoto Y,.and Miki T.: "Orthostatic hypertension : another orthostatic disorder to be aware of."J Am Geriatr Soc. 48. 1538-1539 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tabara Y.,Kohara K.and Miki T.: "Risk factor-gene interaction in caroid atherosclerosis : Effect of gene polymorphisms of renin-angiotension system."J Hum.Genet. (in press). (2001)

    • Related Report
      2000 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi