RGD Reference Report - The gene encoding atrial natriuretic peptide and the risk of human stroke. - Rat Genome Database

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The gene encoding atrial natriuretic peptide and the risk of human stroke.

Authors: Rubattu, S  Ridker, P  Stampfer, M J  Volpe, M  Hennekens, C H  Lindpaintner, K 
Citation: Rubattu S, etal., Circulation. 1999 Oct 19;100(16):1722-6. doi: 10.1161/01.cir.100.16.1722.
RGD ID: 149735577
Pubmed: PMID:10525492   (View Abstract at PubMed)
DOI: DOI:10.1161/01.cir.100.16.1722   (Journal Full-text)


BACKGROUND: Recent evidence from an animal model of stroke, the stroke-prone spontaneously hypertensive rat, implicated the gene encoding atrial natriuretic peptide (ANP) as a possible candidate contributing to the likelihood of experiencing a stroke. The purpose of the present study was to investigate the role of ANP in the pathogenesis of cerebrovascular accidents in humans.
METHODS AND RESULTS: We investigated 2 previously known markers at ANP, G1837A and T2238C, for their possible association with the occurrence of stroke. This was the largest matched case-controlled sample studied thus far; the sample was drawn from a large prospective study (the Physician's Health Study). When assuming a dominant mode of inheritance, a statistically significant positive association was observed for the 1837A allele, indicating an odds ratio of 1.64 (95% confidence interval, 1.01 to 2.65) for stroke. This observation led to the discovery of a new molecular variant in exon 1, G664A, which was responsible for a valine-to-methionine substitution in the proANP peptide. This mutation, which was in linkage disequilibrium with the G1837A marker, was associated with the occurrence of stroke (odds ratio, 2.0; 95% confidence interval, 1.17 to 3.19; P=0.01).
CONCLUSIONS: Our findings suggest that molecular variants of the ANP gene may represent an independent risk factor for cerebrovascular accidents in humans. The strong parallelism to the experimental data obtained in the stroke-prone animal model provides assurance for the relevance of our observation.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NPPAHumanStroke susceptibilityIAGP DNA:SNP more ...RGD 
NppaRatStroke susceptibilityISONPPA (Homo sapiens)DNA:SNP more ...RGD 
NppaMouseStroke susceptibilityISONPPA (Homo sapiens)DNA:SNP more ...RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NPPAHumanDiabetes mellitus susceptibilityIAGP DNA:SNP more ...RGD 
NPPAHumanElevated diastolic blood pressure susceptibilityIAGP DNA:SNP more ...RGD 
NPPAHumanElevated systolic blood pressure susceptibilityIAGP DNA:SNP more ...RGD 
NPPAHumanIncreased body mass index susceptibilityIAGP DNA:SNP more ...RGD 
NPPAHumanStroke susceptibilityIAGP DNA:SNP more ...RGD 
Objects Annotated

Genes (Rattus norvegicus)
Nppa  (natriuretic peptide A)

Genes (Mus musculus)
Nppa  (natriuretic peptide type A)

Genes (Homo sapiens)
NPPA  (natriuretic peptide A)


Additional Information