RGD Reference Report - Splicing mutation of the prostacyclin synthase gene in a family associated with hypertension. - Rat Genome Database

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Splicing mutation of the prostacyclin synthase gene in a family associated with hypertension.

Authors: Nakayama, T  Soma, M  Watanabe, Y  Hasimu, B  Sato, M  Aoi, N  Kosuge, K  Kanmatsuse, K  Kokubun, S  Marrow, JD  Oates, JA 
Citation: Nakayama T, etal., Biochem Biophys Res Commun 2002 Oct 11;297(5):1135-9.
RGD ID: 1298040
Pubmed: PMID:12372404   (View Abstract at PubMed)

Prostacyclin inhibits platelet aggregation, smooth muscle cell proliferation, and vasoconstriction. The prostacyclin synthase (PGIS) gene is a candidate gene for cardiovascular disease. The purpose of this study was to locate possible mutations in the PGIS gene related to hypertension and cerebral infarction. Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method, we discovered a T to C transition at the +2 position of the splicing donor site of intron 9 in patients with essential hypertension (EH). In vitro expression analysis of an allelic minigene consisting of exons 8-10 revealed that the nucleotide transition causes skipping of exon 9. This in turn alters the translational reading frame of exon 10 and introduces a premature stop codon (TGA). A three-dimensional model shows that the splice site mutation produces a truncated protein with a deletion in the heme-binding region. This splice site mutation was found in only one subject in 200 EH patients and 200 healthy controls. Analysis of the patient's family members revealed the mutation in two of the three siblings. The urinary excretion of prostacyclin metabolites in subjects with the mutation was significantly decreased. All subjects displaying the splice site mutation in the PGIS gene were hypertensive. In this study, we report a novel splicing mutation in the PGIS gene, which is associated with hypertension in a family. It is thought that this mechanism may involve in the pathophysiology of their hypertension.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BP29_HHumanhypertension  IDA  RGD 
PTGISHumanhypertension  IAGP  RGD 
PtgisRathypertension  ISOPTGIS (Homo sapiens) RGD 
PtgisMousehypertension  ISOPTGIS (Homo sapiens) RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BP29_HHumanElevated mean arterial pressure  QTM  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Ptgis  (prostaglandin I2 synthase)

Genes (Mus musculus)
Ptgis  (prostaglandin I2 (prostacyclin) synthase)

Genes (Homo sapiens)
PTGIS  (prostaglandin I2 synthase)

BP29_H  (Blood pressure QTL 29 (human))

Additional Information