INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis.

<h4>Background</h4>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...

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Autores principales:	Yan Liu, Hanna K Sanoff, Hyunsoon Cho, Christin E Burd, Chad Torrice, Karen L Mohlke, Joseph G Ibrahim, Nancy E Thomas, Norman E Sharpless
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/37e7e80ef505417bac949e65119c4be0
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spelling	oai:doaj.org-article:37e7e80ef505417bac949e65119c4be02021-11-25T06:16:19ZINK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis.1932-620310.1371/journal.pone.0005027https://doaj.org/article/37e7e80ef505417bac949e65119c4be02009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19343170/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.Yan LiuHanna K SanoffHyunsoon ChoChristin E BurdChad TorriceKaren L MohlkeJoseph G IbrahimNancy E ThomasNorman E SharplessPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 4, p e5027 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yan Liu Hanna K Sanoff Hyunsoon Cho Christin E Burd Chad Torrice Karen L Mohlke Joseph G Ibrahim Nancy E Thomas Norman E Sharpless INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.
format	article
author	Yan Liu Hanna K Sanoff Hyunsoon Cho Christin E Burd Chad Torrice Karen L Mohlke Joseph G Ibrahim Nancy E Thomas Norman E Sharpless
author_facet	Yan Liu Hanna K Sanoff Hyunsoon Cho Christin E Burd Chad Torrice Karen L Mohlke Joseph G Ibrahim Nancy E Thomas Norman E Sharpless
author_sort	Yan Liu
title	INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis.
title_short	INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis.
title_full	INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis.
title_fullStr	INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis.
title_full_unstemmed	INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis.
title_sort	ink4/arf transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/37e7e80ef505417bac949e65119c4be0
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INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis.

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