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Upstream Transcription Factor 1 (USF1) allelic variants regulate lipoprotein metabolism in women and USF1 expression in atherosclerotic plaque. 2014
Yue-Mei Fan, and
Jussi Hernesniemi, and
Niku Oksala, and
Mari Levula, and
Emma Raitoharju, and
Auni Collings, and
Nina Hutri-Kähönen, and
Markus Juonala, and
Jukka Marniemi, and
Leo-Pekka Lyytikäinen, and
Ilkka Seppälä, and
Ari Mennander, and
Matti Tarkka, and
Antti J Kangas, and
Pasi Soininen, and
Juha Pekka Salenius, and
Norman Klopp, and
Thomas Illig, and
Tomi Laitinen, and
Mika Ala-Korpela, and
Reijo Laaksonen, and
Jorma Viikari, and
Mika Kähönen, and
Olli T Raitakari, and
Terho Lehtimäki
Department of Clinical Chemistry, Fimlab Laboratories, Tampere University Hospital and School of Medicine at the University of Tampere, Tampere.
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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