title: CDKN2B expression and subcutaneous adipose tissue expandability: possible influence of the 9p21 atherosclerosis locus.
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.
authors.affiliation: Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Sweden.
authors.forename: Per-Arne
authors.initials: PA
authors.lastname: Svensson
authors.affiliation: Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Wahlstrand
authors.affiliation: Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Sweden.
authors.forename: Maja
authors.initials: M
authors.lastname: Olsson
authors.affiliation: Department of Genomics of Common Disease, School of Public Health, Imperial College London, UK.
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.affiliation: Department of Genomics of Common Disease, School of Public Health, Imperial College London, UK.
authors.forename: Mario
authors.initials: M
authors.lastname: Falchi
authors.affiliation: Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Bergman
authors.affiliation: Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: Philip G
authors.initials: PG
authors.lastname: McTernan
authors.affiliation: Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hedner
authors.affiliation: Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Sweden.
authors.forename: Lena M S
authors.initials: LM
authors.lastname: Carlsson
authors.affiliation: Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, Sweden. Electronic address: peter.jacobson@medfak.gu.se.
authors.forename: Peter
authors.initials: P
authors.lastname: Jacobson
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism; D015992:Body Mass Index; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics* / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D005786:Gene Expression Regulation; D056426:Genetic Loci; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D050151:Subcutaneous Fat / Q000378:metabolism*
chemical_list: D050762:Cyclin-Dependent Kinase Inhibitor p15
keywords: Adipose tissue; CDKN2B; Chromosome 9p21