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

作者：Fan Yue Mei^*; Hernesniemi Jussi; Oksala Niku; Levula Mari; Raitoharju Emma; Collings Auni; Hutri Kahonen Nina; Juonala Markus; Marniemi Jukka; Lyytikainen Leo Pekka; Seppala Ilkka; Mennander Ari; Tarkka Matti; Kangas Antti J; Soininen Pasi; Salenius Juha Pekka; Klopp Norman; Illig Thomas; Laitinen Tomi; Ala Korpela Mika; Laaksonen Reijo; Viikari Jorma; Kahonen Mika; Raitakari Olli T; Lehtimaki Terho

来源：Scientific Reports, 2014, 4(1): 4650.

DOI：10.1038/srep04650

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 %26lt; CT %26lt; CC and rs1556259AA %26lt; AG %26lt; GGas well as according to USF1 H3 (GCCCGG) copy number 0 %26lt; 1 %26lt; 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.

• 出版日期2014-4-11