| SNPs in MicroRNA Binding Sites in 3'-UTRs of RAAS Genes Influence Arterial Blood Pressure and Risk of Myocardial Infarction. | |
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MedLine Citation:
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PMID: 21677697 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BackgroundWe hypothesized that single nucleotide polymorphisms (SNPs) located in microRNA (miR) binding sites in genes of the renin angiotensin aldosterone system (RAAS) can influence blood pressure and risk of myocardial infarction.MethodsUsing online databases dbSNP and TargetScan, we identified 10 SNPs in potential miR binding sites in eight RAAS-related genes, common in Caucasians. We genotyped a large case-control study on myocardial infarctions, the Study of Myocardial Infarctions LEiden (SMILE) for these 10 SNPs and found nine SNPs, in seven genes, to be prevalent. Functionality of each SNP in interfering with mRNA/miR binding was tested using a dual luciferase reporter gene system.ResultsOf these nine SNPs, four SNPs, located in the arginine vasopressin 1A receptor (AVPR1A), bradykinin 2 receptor (BDKRB2), and thromboxane A2 receptor (TBXA2R) genes were associated with blood pressure. The rare allele of the AVPR1A SNP rs11174811, was associated with increased blood pressure whereas the rare alleles of the two linked BDKRB2 SNPs rs5225 and rs2069591 and of the TBXA2R SNP rs13306046 were associated with decreased blood pressure. Although not associated with blood pressure, the rare allele of the mineralocorticoid receptor (NR3C2) SNP rs5534, was associated with a twofold increased risk of myocardial infarction in men younger than 50 years. For all of these five SNPs, except rs2069591, we could demonstrate a reduction in miR-induced repression of gene expression.ConclusionsCommon SNPs in miR binding sites of RAAS-related genes can influence both blood pressure and risk of myocardial infarction. These results may imply an important role for SNPs in miR target sites in human disease.American Journal of Hypertension (2011). doi:10.1038/ajh.2011.92. |
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Authors:
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A Yaël Nossent; Jakob L Hansen; Carine Doggen; Paul Ha Quax; Søren P Sheikh; Frits R Rosendaal |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-6-16 |
Journal Detail:
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Title: American journal of hypertension Volume: - ISSN: 1879-1905 ISO Abbreviation: - Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-6-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8803676 Medline TA: Am J Hypertens Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] Department for Biochemistry, Pharmacology and Genetics, Odense University Hospital, Odense, Denmark [2] Laboratory for Molecular Cardiology, The Danish National Research Foundation Centre for Cardiac Arrhythmia, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark [3] The Heart Centre, Copenhagen University Hospital, Copenhagen, Denmark [4] Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands [5] Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands. |
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