title: SNPs in microRNA binding sites in 3'-UTRs of RAAS genes influence arterial blood pressure and risk of myocardial infarction.
abstract: BACKGROUND
  We 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.
  
  
  METHODS
  Using 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.
  
  
  RESULTS
  Of 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.
  
  
  CONCLUSIONS
  Common 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.
authors.affiliation: Department for Biochemistry, Pharmacology and Genetics, Odense University Hospital, Odense, Denmark.
authors.forename: A Yaël
authors.initials: AY
authors.lastname: Nossent
authors.forename: Jakob L
authors.initials: JL
authors.lastname: Hansen
authors.forename: Carine
authors.initials: C
authors.lastname: Doggen
authors.forename: Paul H A
authors.initials: PH
authors.lastname: Quax
authors.forename: Søren P
authors.initials: SP
authors.lastname: Sheikh
authors.forename: Frits R
authors.initials: FR
authors.lastname: Rosendaal
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics / Q000502:physiology; D001665:Binding Sites / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology; D005169:Factor VIII / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009203:Myocardial Infarction / Q000209:etiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D043782:Receptor, Bradykinin B2 / Q000235:genetics; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000235:genetics; D017483:Receptors, Vasopressin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics* / Q000502:physiology; D014841:von Willebrand Factor / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D043782:Receptor, Bradykinin B2; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D017483:Receptors, Vasopressin; D014841:von Willebrand Factor; D005169:Factor VIII