Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants.

<h4>Background</h4>Several genome-wide association studies have recently linked a group of single nucleotide polymorphisms in the 9p21 region with cardiovascular disease. The molecular mechanisms of this link are not fully understood. We investigated five different expression microarray...

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Autores principales: Lasse Folkersen, Theodosios Kyriakou, Anuj Goel, John Peden, Anders Mälarstig, Gabrielle Paulsson-Berne, Anders Hamsten, Hugh Watkins, Anders Franco-Cereceda, Anders Gabrielsen, Per Eriksson, PROCARDIS consortia
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Publicado: Public Library of Science (PLoS) 2009
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spelling oai:doaj.org-article:4e6a32a404894831a2dc98e5e9b686a02021-11-25T06:28:23ZRelationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants.1932-620310.1371/journal.pone.0007677https://doaj.org/article/4e6a32a404894831a2dc98e5e9b686a02009-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19888323/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Several genome-wide association studies have recently linked a group of single nucleotide polymorphisms in the 9p21 region with cardiovascular disease. The molecular mechanisms of this link are not fully understood. We investigated five different expression microarray datasets in order to determine if the genotype had effect on expression of any gene transcript in aorta, mammary artery, carotid plaque and lymphoblastoid cells.<h4>Methodology/principal findings</h4>After multiple testing correction, no genes were found to have relation to the rs2891168 risk genotype, either on a genome-wide scale or on a regional (8 MB) scale. The neighbouring ANRIL gene was found to have eight novel transcript variants not previously known from literature and these varied by tissue type. We therefore performed a detailed probe-level analysis and found small stretches of significant relation to genotype but no consistent associations. In all investigated tissues we found an inverse correlation between ANRIL and the MTAP gene and a positive correlation between ANRIL and CDKN2A and CDKN2B.<h4>Conclusions/significance</h4>Investigation of relation of the risk genotype to gene expression is complicated by the transcript complexity of the locus. With our investigation of a range of relevant tissue we wish to underscore the need for careful attention to the complexity of the alternative splicing issues in the region and its implications to the design of future gene expression studies.Lasse FolkersenTheodosios KyriakouAnuj GoelJohn PedenAnders MälarstigGabrielle Paulsson-BerneAnders HamstenHugh WatkinsAnders Franco-CerecedaAnders GabrielsenPer ErikssonPROCARDIS consortiaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 11, p e7677 (2009)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Lasse Folkersen
Theodosios Kyriakou
Anuj Goel
John Peden
Anders Mälarstig
Gabrielle Paulsson-Berne
Anders Hamsten
Hugh Watkins
Anders Franco-Cereceda
Anders Gabrielsen
Per Eriksson
PROCARDIS consortia
Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants.
description <h4>Background</h4>Several genome-wide association studies have recently linked a group of single nucleotide polymorphisms in the 9p21 region with cardiovascular disease. The molecular mechanisms of this link are not fully understood. We investigated five different expression microarray datasets in order to determine if the genotype had effect on expression of any gene transcript in aorta, mammary artery, carotid plaque and lymphoblastoid cells.<h4>Methodology/principal findings</h4>After multiple testing correction, no genes were found to have relation to the rs2891168 risk genotype, either on a genome-wide scale or on a regional (8 MB) scale. The neighbouring ANRIL gene was found to have eight novel transcript variants not previously known from literature and these varied by tissue type. We therefore performed a detailed probe-level analysis and found small stretches of significant relation to genotype but no consistent associations. In all investigated tissues we found an inverse correlation between ANRIL and the MTAP gene and a positive correlation between ANRIL and CDKN2A and CDKN2B.<h4>Conclusions/significance</h4>Investigation of relation of the risk genotype to gene expression is complicated by the transcript complexity of the locus. With our investigation of a range of relevant tissue we wish to underscore the need for careful attention to the complexity of the alternative splicing issues in the region and its implications to the design of future gene expression studies.
format article
author Lasse Folkersen
Theodosios Kyriakou
Anuj Goel
John Peden
Anders Mälarstig
Gabrielle Paulsson-Berne
Anders Hamsten
Hugh Watkins
Anders Franco-Cereceda
Anders Gabrielsen
Per Eriksson
PROCARDIS consortia
author_facet Lasse Folkersen
Theodosios Kyriakou
Anuj Goel
John Peden
Anders Mälarstig
Gabrielle Paulsson-Berne
Anders Hamsten
Hugh Watkins
Anders Franco-Cereceda
Anders Gabrielsen
Per Eriksson
PROCARDIS consortia
author_sort Lasse Folkersen
title Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants.
title_short Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants.
title_full Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants.
title_fullStr Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants.
title_full_unstemmed Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants.
title_sort relationship between cad risk genotype in the chromosome 9p21 locus and gene expression. identification of eight new anril splice variants.
publisher Public Library of Science (PLoS)
publishDate 2009
url https://doaj.org/article/4e6a32a404894831a2dc98e5e9b686a0
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