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Splicing Mutation of the Prostacyclin Synthase Gene in a Family Associated with Hypertension

  • Tomohiro Nakayama
  • Masayoshi Soma
  • Yoshiyasu Watanabe
  • Buaijiaer Hasimu
  • Katsuo Kanmatsuse
  • Shinichiro Kokubun
  • Jason D. Morrow
  • John A. Oates
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 525)

Abstract

Prostacyclin inhibits platelet aggregation, and vasoconstriction [1]. Prostacyclin synthase (PGIS, CYP 8A1, EC 5.3.99.4), a catalyst of prostacyclin formation from prostaglandin H2, is widely distributed and predominantly found in vascular endothelial and smooth muscle cells [2]. The PGIS gene is localized to 20ql3.11-13 and thought to be a candidate gene for cardiovascular disease. We reported the organization of this gene [3]. Furthermore, we identified a family with a nonsense mutation in exon 2 of the prostacyclin synthase gene, and this family displays a history of hypertension and cerebral infarction [4]. These findings suggested that abnormality of the prostacyclin synthase gene may lead to altered vasodilation and platelet aggregation.

Keywords

Essential Hypertension Splice Site Mutation Splice Mutation Urinary Creatinine Excretion Essential Hypertension Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Moncada S, Gryglewski RJ, Bunting S, Vane JR. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 1976; 263:663–665.PubMedCrossRefGoogle Scholar
  2. 2.
    Oates JA, FitzGerald GA, Branch RA. Clinical implications of prostaglandin and thromboxane A2 formation. New Eng J Med 1988; 319:689–717.PubMedCrossRefGoogle Scholar
  3. 3.
    Nakayama T, Soma M, Izumi Y, Kanmatsuse K. Organization of the human prostacyclin synthase gene. Biochem Biophys Res Commun 1996; 221:803–806.PubMedCrossRefGoogle Scholar
  4. 4.
    Nakayama T, Soma M, Rahmutula D, Izumi Y, Kanmatsuse K. Nonsense mutation of prostacyclin synthase gene in a family. Lancet 1997; 349:1887–1888.PubMedCrossRefGoogle Scholar
  5. 5.
    Shyue SK, Ruan KH, Wang LH, Wu KK. Prostacyclin synthase active sites. Identification by molecular modeling-guided site-directed mutagenesis. J Biol Chem 1997; 272:3657–62.PubMedCrossRefGoogle Scholar
  6. 6.
    Hatae T, Hara S, Yokoyama C, Yabuki T, Inoue H, Ullrich V, Tanabe T. Site-directed mutagenesis of human prostacyclin synthase: Alteration of Cys441 of the Cys-pocket, and Glu347 and Arg350 of the EXXR motif FEBS Lett 1996; 389:268–72.Google Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Tomohiro Nakayama
    • 1
  • Masayoshi Soma
    • 2
  • Yoshiyasu Watanabe
    • 2
  • Buaijiaer Hasimu
    • 2
  • Katsuo Kanmatsuse
    • 2
  • Shinichiro Kokubun
    • 1
  • Jason D. Morrow
    • 3
  • John A. Oates
    • 4
  1. 1.Division of Receptor Biology, Advanced Medical Research CenterNihon University School of MedicineItabashi-kuJapan
  2. 2.Second Internal MedicineNihon University School of MedicineItabashi-kuJapan
  3. 3.Department of PharmacologyVanderbilt University School of MedicineNashvilleUSA
  4. 4.Division of Clinical PharmacologyVanderbilt University School of Medicine, The Vanderbilt-Ingram Cancer CenterNashvilleUSA

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