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2010 Fiscal Year Final Research Report

Does polymorphism of metabolic syndrome-related genes induce lower urinary tract symptoms?

Research Project

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Project/Area Number 20390422
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionUniversity of Fukui

Principal Investigator

YOKOYAMA Osamu  University of Fukui, 医学部, 教授 (90242552)

Co-Investigator(Kenkyū-buntansha) AKINO Hironobu  福井大学, 医学部, 准教授 (90159335)
AOKI Yoshitaka  福井大学, 医学部, 助教 (30273006)
YOKOTA Yoshifumi  福井大学, 医学部, 教授 (50222386)
KUSUKAWA Naoya  福井大学, 医学部, 医員 (80372499)
Project Period (FY) 2008 – 2010
Keywordsメタボリック症候群 / 遺伝子多型 / 下部尿路症状 / COX-2
Research Abstract

We investigated the relationship between polymorphism of metabolic syndrome-related gene and occurrence of lower urinary tract symptoms, using human blood samples and animal pathological models.
Organ ischemia is thought to be caused by matrix digestion by metalloproteinases (MMPs) leading to rupture of atherosclerotic plaques. Production of macrophage MMP-2 and MMP-9 is induced by cycloxygenase-2 (COX-2) and prostaglandin E2 (PGE2) synthesis. The-765G->C polymorphism of the COX-2 gene has been reported to associate with a decrease risk of myocardial infarction and stroke. Detection of this genotype may be useful to predicting genetic risk of bladder storage dysfunction because bladder ischemia is known as one of the important risks for lower urinary tract symptoms (CUTS). Using blood samples of patients with overactive bladder (OAB), the-765G->Cvariant was genotyped. As the prevalence of the variant was low in these patients, the significant relationship was not found. Next, to investi … More gate the association between the urinary levels of PGE2, PGF2α, nerve growth factor (NGF) and substance P, and OAB symptoms, urine samples from 114 patients in the chronic phase of a brain disease and 27 healthy controls were analyzed by enzyme-linked immunosorbent assay. As a result, the urinary PGE2 level was putatively elevated in patients with suprapontine brain diseases and associated with the presence of OAB. We collected data on 28,238 individuals (9,286 males and 18,952 females) who participated in a multiphasic health screening in Fukui, Japan. The overall prevalence of nocturia (defined as two or more voids/night) was 5.8%. In the multivariate analysis, a significant association was found between nocturia and the followings:age, male gender, BMI<18.5, BMI>27.0, high blood pressure and impaired glucose tolerance. The number of components of MetS was correlated with nocturia.
Using rat animal models with cerebral infarction (CI), we investigated the underlying mechanism of increase in the urinary PGE2 level in patients with suprapontine brain diseases. The ATP amount in the bladder of CI rats was 2.24 times larger than that of sham operated(SO) rats 6 hours after CI. Compared with SO rats, the mRNA expression of P2X3, ASIC2, TRPV1, M2 and M3 in the bladder wall increased after CI, meaning upregulation of C fiber afferent nerves of the bladder. These changes were not found in rats pretreated with resiniferatoxin.
As an animal model of metabolic syndrome, rats were fed with fructose-rich diet for 11 months. Rats revealed hypertension, glucose intolerance, and frequent voiding. The expression of COX-2 in the bladder wall was found to increase in these rats. Less

  • Research Products

    (25 results)

All 2011 2010 2009 2008 Other

All Journal Article (17 results) (of which Peer Reviewed: 17 results) Presentation (8 results)

  • [Journal Article] Modulation of Stretch-evoked Adenosine Triphosphate Release from the Bladder Epithelium by Prostaglandin E22011

    • Author(s)
      Tanaka I, Nagase K, Tanase K, Aoki Y, Akino H, Yokoyama O.
    • Journal Title

      J Urol 185

      Pages: 341

    • Peer Reviewed
  • [Journal Article] Improvement of non-inflamatory detrusor overactivity through supressionof peripheral C-fiber by cyclooxygenase inhibitors.2010

    • Author(s)
      Tanaka I, Nagase K, Tanase K, Aoki Y, Akino H, Yokoyama O.
    • Journal Title

      J Urol 183

      Pages: 786-792

    • Peer Reviewed
  • [Journal Article] Pharmacologic and Genetic Analysis of Mechanisms Underlying Detrusor overactivity in rats.2010

    • Author(s)
      Yokoyama O.
    • Journal Title

      Neurourol Urodyn 29

      Pages: 107-111

    • Peer Reviewed
  • [Journal Article] Influence of Urethral Sphincter Incompetence on Bladder Shape and Function in Myelodysplastic Children.2010

    • Author(s)
      Yokoyama O, Ito H, Namiki M.
    • Journal Title

      LUTS 2

      Pages: 27-30

    • Peer Reviewed
  • [Journal Article] Selective α1A-blocker improves bladder storage function in rats via suppression of C-fiber afferent activity.2010

    • Author(s)
      Yokoyama O, Ito H, Aoki Y, Oyama N, Miwa Y, Akino H.
    • Journal Title

      World J Urol 28

      Pages: 609-614

    • Peer Reviewed
  • [Journal Article] Zolpidem increases bladder capacity and decreases urine excretion in rats.2010

    • Author(s)
      Yokoyama O, Matsuta Y, Yanai-Inamura H, Watanabe M, Ohtake A,, Suzuki M, Sasamata M.
    • Journal Title

      Neurourol Urodyn 29

      Pages: 107-111

    • Peer Reviewed
  • [Journal Article] Urinary Prostaglandin E(2) was increased in patients with suprapontine brain diseases, and associated with overactive bladder syndrome.2010

    • Author(s)
      Yamauchi H, Akino H, Ito H, Aoki Y, Nomura T, Yokoyama O.
    • Journal Title

      Urology in press

    • Peer Reviewed
  • [Journal Article] Melatonin increases bladder capacity via GABAergic system and decreases urine volume in rats.2010

    • Author(s)
      Matsuta Y, Yusup A, Tanase K, Ishida H, Akino H, Yokoyama O.
    • Journal Title

      J Urol 184

      Pages: 386-391

    • Peer Reviewed
  • [Journal Article] Animal model with detrusor overactivity caused by cerebral infarction as a useful tool for pharmacological therapeutic approaches.2009

    • Author(s)
      Yokoyama O, Ishiura Y, Nakamura Y.
    • Journal Title

      LUTS 1

      Pages: 98-100

    • Peer Reviewed
  • [Journal Article] Neurogenic Bladder Society Clinical guidelines for overactive bladder.2009

    • Author(s)
      Yamaguchi O, Nishizawa O, Takeda M, Yokoyama O, Homma Y, Kakizaki H, Obara K, Gotoh M, Igawa Y, Seki N, Yoshida M
    • Journal Title

      Int J Urol 16

      Pages: 126-142

    • Peer Reviewed
  • [Journal Article] Clinical guideline for male lower urinary tract symptoms.2009

    • Author(s)
      Homma Y, Araki I, Igawa Y, Ozono S, Gotoh M, Yamanishi T, Yokoyama O, Yoshida M.
    • Journal Title

      Int J Urol 16

      Pages: 775-790

    • Peer Reviewed
  • [Journal Article] Neurogenic Bladder Society. Clinical guidelines for overactive bladder.2009

    • Author(s)
      Yamaguchi O, Nishizawa O, Takeda M, Yokoyama O, Homma Y, Kakizaki H, Obara K, Gotoh M, Igawa Y, Seki N, Yoshida M.
    • Journal Title

      Int J Urol 16

      Pages: 126-142

    • Peer Reviewed
  • [Journal Article] Spontaneous contractions of the pig urinary bladder : the effect of ATP-sensitive potassium channels and the role of the mucosa.2008

    • Author(s)
      Akino H, Chapple CR, McKay N, Cross RL, Murakami S, Yokoyama O, Chess-Williams R, Sellers DJ.
    • Journal Title

      BJU Int 102

      Pages: 1168-1174

    • Peer Reviewed
  • [Journal Article] Ultrasound-estimated bladder weight predicts risk of surgery for benign prostatic hyperplasia in men using alpha-adrenoceptor blocker for LUTS.2008

    • Author(s)
      Akino H, Maekawa M, Nakai M, Shioyama R, Ishida H, Oyama N, Miwa Y, Yokoyama O.
    • Journal Title

      Urology 72

      Pages: 817-820

    • Peer Reviewed
  • [Journal Article] Association between lower urinary tract symptoms and serum levels of sex hormones in men.2008

    • Author(s)
      Miwa Y, Kaneda T, Yokoyama O.
    • Journal Title

      Urology 72

      Pages: 552-555

    • Peer Reviewed
  • [Journal Article] Long-lasting breaches in the bladder epithelium lead to storage dysfunction with increase in bladder PGE2 levels in the rat.2008

    • Author(s)
      Shioyama R, Aoki Y, Ito H, Matsuta Y, Nagase K, Oyama N, Miwa Y, Akino H, Imamura Y, Yokoyama O.
    • Journal Title

      Am J Physiol Regul Integr Comp Physiol 295

      Pages: 714-718

    • Peer Reviewed
  • [Journal Article] alpha(1)-Adrenoceptor blocker naftopidil improves sleep disturbance with reduction in nocturnal urine volume.

    • Author(s)
      Yokoyama O, Aoki Y, Tsujimura A, Takao T, Namiki M, Okuyama.
    • Journal Title

      World J Urol In press

    • Peer Reviewed
  • [Presentation] Epidemiology in men's health.2010

    • Author(s)
      横山修
    • Organizer
      5^<th> Japan-Asean Conference on Men's Health and Aging.
    • Place of Presentation
      Kota Kinabalu, Malaysia
    • Year and Date
      2010-07-10
  • [Presentation] Understanding the Science, 30th Congress of the Societe Internationale d'Urologie2009

    • Author(s)
      横山修
    • Organizer
      Counting the Cost of OAB and Its Burden on Society
    • Place of Presentation
      Shanghai(CHN)
    • Year and Date
      2009-11-05
  • [Presentation] Relationship between nocturia and metabolic syndrome2009

    • Author(s)
      Aoki Y, Kusukawa N, Matsuta Y, Maegawa M, Tanase K, Ito H, Oyama N, Miwa Y, Akino H, Yokoyama O
    • Organizer
      International Continence Society 39th Annual Meeting
    • Place of Presentation
      San Francisco(USA)
    • Year and Date
      2009-10-03
  • [Presentation] 下部尿路症状とメタボリック症候群との関連について2009

    • Author(s)
      横山修
    • Organizer
      第16回日本排尿機能学会, ランチョンセミナー1
    • Place of Presentation
      福岡
    • Year and Date
      2009-09-12
  • [Presentation] Erectile dysfunction and lower urinary tract symptoms:possible pathophysiological relation to vascular function2009

    • Author(s)
      横山修
    • Organizer
      4th Japan and Korea Satellite Symposium
    • Place of Presentation
      Toyama
    • Year and Date
      2009-07-02
  • [Presentation] Is female nocturia associated with metabolic syndrome?2009

    • Author(s)
      Aoki Y, Takahara N, Tanase K, Ito H, Oyama N, Miwa Y, Akino H, Yokoyama O
    • Organizer
      2009 Annual Meeting of American Urological Association
    • Place of Presentation
      Chicago(USA)
    • Year and Date
      2009-04-28
  • [Presentation] What is the most valuable mediator secreted from the urothelium of the urinary bladder in patients with neurogenic overactive bladder?2009

    • Author(s)
      Yamauchi H, Ito H, Aoki Y, Akino H, Yokoyama O, Nomura T
    • Organizer
      2009 Annual Meeting of American Urological Association
    • Place of Presentation
      Chicago(USA)
    • Year and Date
      2009-04-27
  • [Presentation] Hypertension as a risk for storage symptom, but not voiding symptom-clinical and experimental studies2009

    • Author(s)
      横山修
    • Organizer
      24th Annual EAU Congress, UROLOGY BEYOND EUROPE
    • Place of Presentation
      Stockholm(SWE)
    • Year and Date
      2009-03-17

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Published: 2012-01-26   Modified: 2016-04-21  

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