title: Blood hsa-miR-122-5p and hsa-miR-885-5p levels associate with fatty liver and related lipoprotein metabolism-The Young Finns Study.
abstract: MicroRNAs are involved in disease development and may be utilized as biomarkers. We investigated the association of blood miRNA levels and a) fatty liver (FL), b) lipoprotein and lipid pathways involved in liver lipid accumulation and c) levels of predicted mRNA targets in general population based cohort. Blood microRNA profiling (TaqMan OpenArray), genome-wide gene expression arrays and nuclear magnetic resonance metabolomics were performed for Young Finns Study participants aged 34-49 years (n = 871). Liver fat status was assessed ultrasonographically. Levels of hsa-miR-122-5p and -885-5p were up-regulated in individuals with FL (fold change (FC) = 1.55, p = 1.36 * 10-14and FC = 1.25, p = 4.86 * 10-4, respectively). In regression model adjusted with age, sex and BMI, hsa-miR-122-5p and -885-5p predicted FL (OR = 2.07, p = 1.29 * 10-8and OR = 1.41, p = 0.002, respectively). Together hsa-miR-122-5p and -885-5p slightly improved the detection of FL beyond established risk factors. These miRNAs may be associated with FL formation through the regulation of lipoprotein metabolism as hsa-miR-122-5p levels associated with small VLDL, IDL, and large LDL lipoprotein subclass components, while hsa-miR-885-5p levels associated inversely with XL HDL cholesterol levels. Hsa-miR-885-5p levels correlated inversely with oxysterol-binding protein 2 (OSBPL2) expression (r = -0.143, p = 1.00 * 10-4) and suppressing the expression of this lipid receptor and sterol transporter could link hsa-miR-885-5p with HDL cholesterol levels.
authors.affiliation: Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, and University of Tampere, School of Medicine, Tampere, Finland.
authors.forename: Emma
authors.initials: E
authors.lastname: Raitoharju
authors.affiliation: Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, and University of Tampere, School of Medicine, Tampere, Finland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Seppälä
authors.affiliation: Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, and University of Tampere, School of Medicine, Tampere, Finland.
authors.forename: Leo-Pekka
authors.initials: LP
authors.lastname: Lyytikäinen
authors.affiliation: Division of Medicine Turku University Hospital and Department of Medicine, University of Turku, Turku, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Viikari
authors.affiliation: Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.|NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.|Computational Medicine, School of Social and Community Medicine and the Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
authors.affiliation: Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.|NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Pasi
authors.initials: P
authors.lastname: Soininen
authors.affiliation: Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Kangas
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum, German Research Center for Environmental Health, Munich, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Waldenberger
authors.affiliation: Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.|Institute for Human Genetics, Hannover Medical School, Hanover, Germany.
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum, German Research Center for Environmental Health, Munich, Germany.|Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.|Institute for Human Genetics, Hannover Medical School, Hanover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.affiliation: Department of Health, National Institute for Health and Welfare, Helsinki and Turku, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Leiviskä
authors.affiliation: Department of Health, National Institute for Health and Welfare, Helsinki and Turku, Finland.
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Loo
authors.affiliation: Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, and University of Tampere, School of Medicine, Tampere, Finland.|Division of Vascular Surgery, Department of Surgery, Tampere University Hospital, Tampere, Finland.
authors.forename: Niku
authors.initials: N
authors.lastname: Oksala
authors.affiliation: Department of Clinical Physiology, Tampere University Hospital, and School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.affiliation: Department of Pediatrics, University of Tampere and Tampere University Hospital, Tampere, Finland.
authors.forename: Nina
authors.initials: N
authors.lastname: Hutri-Kähönen
authors.affiliation: Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, and University of Tampere, School of Medicine, Tampere, Finland.
authors.forename: Reijo
authors.initials: R
authors.lastname: Laaksonen
authors.affiliation: Research Centre for Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.|Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Raitakari
authors.affiliation: Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, and University of Tampere, School of Medicine, Tampere, Finland.
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005234:Fatty Liver / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D055106:Genome-Wide Association Study; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D014463:Ultrasonography
chemical_list: D008074:Lipoproteins; C531907:MIRN122 microRNA, human; C574934:MIRN885 microRNA, human; D035683:MicroRNAs