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Background  Genome-wide association studies (GWAS) have linked common single nucleotide polymorphisms (SNPs) on chromosome 9p21 near the  INK4/ARF  ( CDKN2A/B ) tumor suppressor locus with risk of atherosclerotic diseases and type 2 diabetes mellitus. To explore the mechanism of this association, we investigated whether expression of proximate transcripts ( p16 INK4a  ,  p15 INK4b  ,  ARF ,  ANRIL  and  MTAP ) correlate with genotype of representative 9p21 SNPs.    Methodology/Principal Findings  We analyzed expression of 9p21 transcripts in purified peripheral blood T-cells (PBTL) from 170 healthy donors. Samples were genotyped for six selected disease-related SNPs spanning the  INK4/ARF  locus. Correlations among these variables were determined by univariate and multivariate analysis. Significantly reduced expression of all  INK4/ARF  transcripts ( p15 INK4b  ,  p16 INK4a  ,  ARF  and  ANRIL ) was found in PBTL of individuals harboring a common SNP (rs10757278) associated with increased risk of coronary artery disease, stroke and aortic aneurysm. Expression of  MTAP  was not influenced by rs10757278 genotype. No association of any these transcripts was noted with five other tested 9p21 SNPs.    Conclusions/Significance  Genotypes of rs10757278 linked to increased risk of atherosclerotic diseases are also associated with decreased expression in PBTL of the  INK4/ARF  locus, which encodes three related anti-proliferative transcripts of known importance in tumor suppression and aging.

INK4/ARF Transcript Expression Is Associated with Chromosome 9p21 Variants Linked to Atherosclerosis