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

被引：187

作者：

Liu, Yan ^{[1
,2
]}

Sanoff, Hanna K. ^{[2
]}

Cho, Hyunsoon ^{[3
]}

Burd, Christin E. ^{[1
,2
]}

Torrice, Chad ^{[1
,2
]}

Mohlke, Karen L. ^{[1
]}

Ibrahim, Joseph G. ^{[3
]}

Thomas, Nancy E. ^{[4
]}

Sharpless, Norman E. ^{[1
,2
]}

机构：

[1] Univ N Carolina, Sch Med, Dept Genet, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27515 USA

[2] Univ N Carolina, Sch Med, Dept Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27515 USA

[3] Univ N Carolina, Sch Med, Dept Biostat, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27515 USA

[4] Univ N Carolina, Sch Med, Dept Dermatol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27515 USA

来源：

PLOS ONE | 2009年 / 4卷 / 04期

关键词：

GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; SMOOTH-MUSCLE-CELLS; GENETIC-VARIATION; P16(INK4A); LOCUS; SENESCENCE; SUSCEPTIBILITY; PROLIFERATION; REPLICATION;

D O I：

10.1371/journal.pone.0005027

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：5

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