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 ISSN 0006-291X.
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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 Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > 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: | Date Event 18 April 2014 Published 25 March 2014 Available 6 March 2014 Submitted |
| 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 (Creative Commons open licence) |
| Date of first compliant deposit: | 27 December 2015 |
| Date of first compliant Open Access: | 27 December 2015 |
| 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) |
| URI: | https://wrap.warwick.ac.uk/60341/ |
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