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CDKN2B expression and subcutaneous adipose tissue expandability : possible influence of the 9p21 atherosclerosis locus

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Svensson, Per-Arne, Wahlstrand, Björn, Olsson, Maja, Froguel, Philippe, Falchi, Mario, Bergman, Richard N., McTernan, P. G., Hedner, Thomas, Carlsson, Lena M. S. and Jacobson, Peter (2014) CDKN2B expression and subcutaneous adipose tissue expandability : possible influence of the 9p21 atherosclerosis locus. Biochemical and Biophysical Research Communications, Volume 446 (Number 4). pp. 1126-1131. doi:10.1016/j.bbrc.2014.03.075

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Official URL: http://dx.doi.org/10.1016/j.bbrc.2014.03.075

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Abstract

Risk alleles within a gene desert at the 9p21 locus constitute the most prevalent genetic determinant of cardiovascular disease. Previous research has demonstrated that 9p21 risk variants influence gene expression in vascular tissues, yet the biological mechanisms by which this would mediate atherosclerosis merits further investigation. To investigate possible influences of this locus on other tissues, we explored expression patterns of 9p21-regulated genes in a panel of multiple human tissues and found that the tumor suppressor CDKN2B was highly expressed in subcutaneous adipose tissue (SAT). CDKN2B expression was regulated by obesity status, and this effect was stronger in carriers of 9p21 risk alleles. Covariation between expression of CDKN2B and genes implemented in adipogenesis was consistent with an inhibitory effect of CDKN2B on SAT proliferation. Moreover, studies of postprandial triacylglycerol clearance indicated that CDKN2B is involved in down-regulation of SAT fatty acid trafficking. CDKN2B expression in SAT correlated with indicators of ectopic fat accumulation, including markers of hepatic steatosis. Among genes regulated by 9p21 risk variants, CDKN2B appears to play a significant role in the regulation of SAT expandability, which is a strong determinant of lipotoxicity and therefore might contribute to the development of atherosclerosis.

Item Type: Journal Article
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016)
Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Cardiovascular system -- Diseases -- Genetic aspects, Adipose tissues
Journal or Publication Title: Biochemical and Biophysical Research Communications
Publisher: Elsevier
ISSN: 0006-291X
Official Date: 18 April 2014
Dates:
DateEvent
18 April 2014Published
25 March 2014Available
6 March 2014Submitted
Volume: Volume 446
Number: Number 4
Page Range: pp. 1126-1131
DOI: 10.1016/j.bbrc.2014.03.075
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
Funder: Swedish Foundation for Strategic Research, Wellcome Trust (London, England), Sweden, European Foundation for the Study of Diabetes (EFSD), Sweden. Vetenskapsrådet [Research Council]
Grant number: GR079534 (WT), K2012-55X-22082-01-3 (SRC), K2010-55X-11285-13 (SRC)

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