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Fan, Y.M.* ; Hernesniemi, J.* ; Oksala, N.* ; Levula, M.* ; Raitoharju, E.* ; Collings, A.* ; Hutri-Kähönen, N.* ; Juonala, M.* ; Marniemi, J.* ; Lyytikäinen, L.-P.* ; Seppälä, I.* ; Mennander, A.* ; Tarkka, M.* ; Kangas, A.J.* ; Soininen, P.* ; Salenius, J.P.* ; Klopp, N. ; Illig, T. ; Laitinen, T.* ; Ala-Korpela, M.* ; Laaksonen, R.* ; Viikari, J.* ; Kähönen, M.* ; Raitakari, O.T.* ; Lehtimäki, T.*

Upstream Transcription Factor 1 (USF1) allelic variants regulate lipoprotein metabolism in women and USF1 expression in atherosclerotic plaque.

Sci. Rep. 4:4650 (2014)
Verlagsversion Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Upstream transcription factor 1 (USF1) allelic variants significantly influence future risk of cardiovascular disease and overall mortality in females. We investigated sex-specific effects of USF1 gene allelic variants on serum indices of lipoprotein metabolism, early markers of asymptomatic atherosclerosis and their changes during six years of follow-up. In addition, we investigated the cis-regulatory role of these USF1 variants in artery wall tissues in Caucasians. In the Cardiovascular Risk in Young Finns Study, 1,608 participants (56% women, aged 31.9 ± 4.9) with lipids and cIMT data were included. For functional study, whole genome mRNA expression profiling was performed in 91 histologically classified atherosclerotic samples. In females, serum total, LDL cholesterol and apoB levels increased gradually according to USF1 rs2516839 genotypes TT < CT < CC and rs1556259 AA < AG < GG as well as according to USF1 H3 (GCCCGG) copy number 0 < 1 < 2. Furthermore, the carriers of minor alleles of rs2516839 (C) and rs1556259 (G) of USF1 gene had decreased USF1 expression in atherosclerotic plaques (P = 0.028 and 0.08, respectively) as compared to non-carriers. The genetic variation in USF1 influence USF1 transcript expression in advanced atherosclerosis and regulates levels and metabolism of circulating apoB and apoB-containing lipoprotein particles in sex-dependent manner, but is not a major determinant of early markers of atherosclerosis.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Familial Combined Hyperlipidemia; Intima-media Thickness; Coronary-artery-disease; Cardiovascular Risk; Young Finns; Myocardial-infarction; Stimulatory Factor-1; Genetic-variants; Heart-failure; Lipid-levels
Sprache englisch
Veröffentlichungsjahr 2014
HGF-Berichtsjahr 2014
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Zeitschrift Scientific Reports
Quellenangaben Band: 4, Heft: , Seiten: , Artikelnummer: 4650 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
POF Topic(s) 30202 - Environmental Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504091-001
PubMed ID 24722012
DOI 10.1038/srep04650
WOS ID WOS:000334102200003
Scopus ID 84898621322
Erfassungsdatum 2014-04-30
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