title: The association of common polymorphisms in miR-196a2 with waist to hip ratio and miR-1908 with serum lipid and glucose.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) have been implicated in the regulation of cardiometabolic disorders. Given the crucial role of miRNAs in gene expression, genetic variation within miRNA genes is expected to affect miRNA function and substantially contribute to disease risk.
  
  
  METHODS
  2,320 variants in miRNA-encoding sequences were systematically retrieved, and their associations with 17 cardiometabolic traits/diseases were investigated, using genome-wide association studies (GWAS) on glycemic indices, anthropometric measures, lipid traits, blood pressure, coronary artery disease, and type 2 diabetes. Next, target genes of the identified miRNAs that may mediate their effect on the phenotypes were examined. Furthermore, trans- expression quantitative trait loci analysis and luciferase reporter assay to provide functional evidence for our findings were performed.
  
  
  RESULTS
  rs11614913:C/T in miR-196a2 was associated with waist to hip ratio (P-value=1.7 × 10(-5) , β = 0.023). Two target genes, SFMBT1 and HOXC8, which may mediate this association were identfied, and they were shown experimentally as direct targets of miR-196a2. Moreover, rs174561:C/T in miR-1908 was found to be associated with total cholesterol (P-value=6.5 × 10(-16) , β=0.044), LDL-cholesterol (P-value=4.3 × 10(-18) , β=0.049), HDL-cholesterol (P-value=1.7 × 10(-6) , β=0.026), triglyceride (P-value=7.8 × 10(-14) , β=0.038), and fasting glucose (P-value=4.3 × 10(-10) , β=0.02). In addition, a number of miR-1908 target genes were highlighted as potential mediators.
  
  
  CONCLUSIONS
  The results indicated miRNA-dependent regulation of fat distribution by miR-196a2 and of lipid metabolism by miR-1908.
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Ghanbari
authors.forename: Sanaz
authors.initials: S
authors.lastname: Sedaghat
authors.forename: Hans W J
authors.initials: HW
authors.lastname: de Looper
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Erkeland
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
authors.forename: Abbas
authors.initials: A
authors.lastname: Dehghan
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D012313:RNA / Q000235:genetics; D049629:Waist-Hip Ratio
chemical_list: D001786:Blood Glucose; D008055:Lipids; C542543:MIRN196 microRNA, human; D035683:MicroRNAs; D012313:RNA