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This study found a significant association between genotype at a CAD risk SNP and reduced expression of CDKN2A, ARF, and CDKN2B in peripheral blood T cells from 170 healthy volunteers. No association with expression of these genes was detected for another CAD risk SNPs in the same population
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Liu Y, Sanoff HK, Cho H, et al.: INK4/ARF Transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis. PLoS One 2009, 4(4): e5027. This study found a significant association between genotype at a CAD risk SNP and reduced expression of CDKN2A, ARF, and CDKN2B in peripheral blood T cells from 170 healthy volunteers. No association with expression of these genes was detected for another CAD risk SNPs in the same population.
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(2009)
PLoS One
, vol.4
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Liu, Y.1
Sanoff, H.K.2
Cho, H.3
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37
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77952363272
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Chromosome 9p21 SNPs associated with multiple disease phenotypes correlate with ANRIL expression
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This study showed that CAD risk alleles were all highly associated with reduced expression of ANRIL in peripheral blood from 487 healthy volunteers, yet only a small proportion were significantly associated with CDKN2A and CDKN2B expression. Most of the variation in total expression levels of these genes was due to trans effects (80%-95%), and although total expression levels of the genes are positively correlated SNPs had inverse effects on ANRIL and CDKN2B expression, supporting a role of antisense transcription in CDKN2B regulation. Multiple SNPs independently influenced ANRIL expression in cis
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Cunnington MS, Santibanez Koref MF, Mayosi BM, et al.: Chromosome 9p21 SNPs associated with multiple disease phenotypes correlate with ANRIL expression. PLoS Genet 2010, 6(4): e1000899. This study showed that CAD risk alleles were all highly associated with reduced expression of ANRIL in peripheral blood from 487 healthy volunteers, yet only a small proportion were significantly associated with CDKN2A and CDKN2B expression. Most of the variation in total expression levels of these genes was due to trans effects (80%-95%), and although total expression levels of the genes are positively correlated SNPs had inverse effects on ANRIL and CDKN2B expression, supporting a role of antisense transcription in CDKN2B regulation. Multiple SNPs independently influenced ANRIL expression in cis.
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(2010)
PLoS Genet
, vol.6
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Cunnington, M.S.1
Santibanez Koref, M.F.2
Mayosi, B.M.3
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38
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Functional analysis of the chromosome 9p21.3 coronary artery disease risk locus
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This study compared whole blood expression of ANRIL, CDKN2A and CDKN2B in 63 healthy individuals homozygous for the 9p21 risk allele and 61 healthy individuals homozygous for the non-risk allele. The risk allele was associated with reduced expression of the long ANRIL transcript and increased expression of short ANRIL transcripts, but there was no significant association with CDKN2A or CDKN2B expression
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Jarinova O, Stewart AFR, Roberts R, et al.: Functional analysis of the chromosome 9p21.3 coronary artery disease risk locus. Arterioscler Thromb Vasc Biol 2009, 29(10): 1671-1677. This study compared whole blood expression of ANRIL, CDKN2A and CDKN2B in 63 healthy individuals homozygous for the 9p21 risk allele and 61 healthy individuals homozygous for the non-risk allele. The risk allele was associated with reduced expression of the long ANRIL transcript and increased expression of short ANRIL transcripts, but there was no significant association with CDKN2A or CDKN2B expression.
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(2009)
Arterioscler Thromb Vasc Biol
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Jarinova, O.1
Stewart, A.F.R.2
Roberts, R.3
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39
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70449555143
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Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. identification of eight new ANRIL splice variants
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This study documented multiple novel ANRIL transcripts in cells derived from different tissues, highlighting the transcript complexity of this locus. No association was found between genotype at an atherosclerosis risk variant and regional or genome-wide expression data in lymphoblastoid cell lines and atherosclerotic tissues
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Folkersen L, Kyriakou T, Goel A, et al.: Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. identification of eight new ANRIL splice variants. PLoS One 2009, 4(11): e7677. This study documented multiple novel ANRIL transcripts in cells derived from different tissues, highlighting the transcript complexity of this locus. No association was found between genotype at an atherosclerosis risk variant and regional or genome-wide expression data in lymphoblastoid cell lines and atherosclerotic tissues.
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(2009)
PLoS One
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Folkersen, L.1
Kyriakou, T.2
Goel, A.3
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40
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Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: Identification of ANRIL, an antisense noncoding RNA whose expression coclusters with ARF
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DOI 10.1158/0008-5472.CAN-06-2004
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Pasmant E, Laurendeau I, Heron D, et al. Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense noncoding rna whose expression coclusters with ARF. Cancer Res. 2007;67(8):3963-9. (Pubitemid 46762186)
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Cancer Research
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Bieche, I.6
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Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10(3):155-9.
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Mercer, T.R.1
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43
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The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells
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DOI 10.1101/gad.415507
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Bracken AP, Kleine-Kohlbrecher D, Dietrich N, et al. The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes Dev. 2007;21(5):525-30. (Pubitemid 46409467)
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Kleine-Kohlbrecher, D.2
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Pasini, D.4
Gargiulo, G.5
Beekman, C.6
Theilgaard-Monch, K.7
Minucci, S.8
Porse, B.T.9
Marine, J.-C.10
Hansen, K.H.11
Helin, K.12
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44
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Expression of the p16(INK4a) tumor suppressor versus other INK4 family members during mouse development and aging
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Zindy F, Quelle DE, Roussel MF, Sherr CJ. Expression of the p16 (INK4a) tumor suppressor versus other INK4 familymembers during mouse development and aging. Oncogene. 1997;15(2):203-11. (Pubitemid 27344559)
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Oncogene
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Zindy, F.1
Quelle, D.E.2
Roussel, M.F.3
Sherr, C.J.4
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45
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77949775636
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Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice
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This study showed that deletion of a 70-kb non-coding region on mouse chromosome 4, which is orthologous to the 9p21 atherosclerosis risk region in humans, was associated with marked reduction of cardiac Cdkn2a and Cdkn2b expression, indicating that distant-acting gene regulatory functions are located in the deleted region. Aortic sooth muscle cells from knockout mice showed excessive proliferation which may contribute to atherosclerosis development
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Visel A, Zhu Y, May D, et al.: Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice. Nature 2010, 464(7287): 409-12. This study showed that deletion of a 70-kb non-coding region on mouse chromosome 4, which is orthologous to the 9p21 atherosclerosis risk region in humans, was associated with marked reduction of cardiac Cdkn2a and Cdkn2b expression, indicating that distant-acting gene regulatory functions are located in the deleted region. Aortic sooth muscle cells from knockout mice showed excessive proliferation which may contribute to atherosclerosis development.
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(2010)
Nature
, vol.464
, Issue.7287
, pp. 409-412
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Visel, A.1
Zhu, Y.2
May, D.3
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46
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77951888636
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p19ARF deficiency reduces macrophage and vascular smooth muscle cell apoptosis and aggravates atherosclerosis
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This study showed that ARF knockout in atherosclerosis-prone apoE-null mice accelerated aortic atheroma development, possibly through attenuated apoptosis of macrophages and vascular smooth muscle cells within atherosclerotic lesions. This supports a direct link between ARF, plaque apoptosis, and atherosclerosis
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González-Navarro H, Abu Nabah YN, Vinué Á, et al.: p19ARF deficiency reduces macrophage and vascular smooth muscle cell apoptosis and aggravates atherosclerosis. J Am Coll Cardiol 2010, 55(20): 2258-2268. This study showed that ARF knockout in atherosclerosis-prone apoE-null mice accelerated aortic atheroma development, possibly through attenuated apoptosis of macrophages and vascular smooth muscle cells within atherosclerotic lesions. This supports a direct link between ARF, plaque apoptosis, and atherosclerosis.
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(2010)
J Am Coll Cardiol
, vol.55
, Issue.20
, pp. 2258-2268
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González-Navarro, H.1
Abu Nabah, Y.N.2
Vinué, Á.3
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47
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38049155825
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Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA
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This study showed that CDKN2B antisense transcription, mapping to the first intron of ANRIL, is associated with down-regulation of CDKN2B expression in leukemia cells and mouse embryonic stem cells, mediated in cis and trans through heterochromatin formation. This suggests that ANRIL may be involved in regulation of CDKN2B expression
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Yu W, Gius D, Onyango P, et al.: Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature 2008, 451 (7175): 202-206. This study showed that CDKN2B antisense transcription, mapping to the first intron of ANRIL, is associated with down-regulation of CDKN2B expression in leukemia cells and mouse embryonic stem cells, mediated in cis and trans through heterochromatin formation. This suggests that ANRIL may be involved in regulation of CDKN2B expression.
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(2008)
Nature
, vol.451
, Issue.7175
, pp. 202-206
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Yu, W.1
Gius, D.2
Onyango, P.3
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48
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77953096072
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Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by Polycomb CBX7 in transcriptional silencing of INK4a
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This study showed that ANRIL specifically interacts with CBX7, a protein within the polycomb repressive complex 1 that represses transcription of CDKN2A and CDKN2B. This suggests a direct role of ANRIL in regulating the expression of these genes
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Yap KL, Li S, Muñoz-Cabello AM, et al.: Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by Polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell 2010, 38(5): 662-674. This study showed that ANRIL specifically interacts with CBX7, a protein within the polycomb repressive complex 1 that represses transcription of CDKN2A and CDKN2B. This suggests a direct role of ANRIL in regulating the expression of these genes.
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(2010)
Mol Cell
, vol.38
, Issue.5
, pp. 662-674
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Yap, K.L.1
Li, S.2
Muñoz-Cabello, A.M.3
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49
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26944461595
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A common variant of CDKN2A (p16) predisposes to breast cancer
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Debniak T, Gorski B, Huzarski T, et al. A common variant of CDKN2A (p16) predisposes to breast cancer. J Med Genet. 2005;42(10):763-5.
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(2005)
J Med Genet
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Debniak, T.1
Gorski, B.2
Huzarski, T.3
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50
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