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Tobacco smoking is associated with methylation of genes related to coronary artery disease
BACKGROUND: Tobacco smoking, a risk factor for coronary artery disease (CAD), is known to modify DNA methylation. We hypothesized that tobacco smoking modifies methylation of the genes identified for CAD by genome-wide association study (GWAS). RESULTS: We selected genomic regions based on 150 singl...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443552/ https://www.ncbi.nlm.nih.gov/pubmed/26015811 http://dx.doi.org/10.1186/s13148-015-0088-y |
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author | Steenaard, Rebecca V Ligthart, Symen Stolk, Lisette Peters, Marjolein J van Meurs, Joyce B Uitterlinden, Andre G Hofman, Albert Franco, Oscar H Dehghan, Abbas |
author_facet | Steenaard, Rebecca V Ligthart, Symen Stolk, Lisette Peters, Marjolein J van Meurs, Joyce B Uitterlinden, Andre G Hofman, Albert Franco, Oscar H Dehghan, Abbas |
author_sort | Steenaard, Rebecca V |
collection | PubMed |
description | BACKGROUND: Tobacco smoking, a risk factor for coronary artery disease (CAD), is known to modify DNA methylation. We hypothesized that tobacco smoking modifies methylation of the genes identified for CAD by genome-wide association study (GWAS). RESULTS: We selected genomic regions based on 150 single-nucleotide polymorphisms (SNPs) identified in the largest GWAS on CAD. We investigated the association between current smoking and the CpG sites within and near these CAD-related genes. Methylation was measured with the Illumina Human Methylation 450K array in whole blood of 724 Caucasian subjects from the Rotterdam Study, a Dutch population based cohort study. A total of 3669 CpG sites within 169 CAD-related genes were studied for association with current compared to never smoking. Fifteen CpG sites were significantly associated after correction for multiple testing (Bonferroni-corrected p value <1.4 × 10(−5)). These sites were located in the genes TERT, SARS, GNGT2, SMG6, SKI, TOM1L2, SIPA1, MRAS, CDKN1A, LRRC2, FES and RPH3A. In 12 sites, current smoking was associated with a 1.2 to 2.4 % lower methylation compared to never smoking; and in three sites, it was associated with a 1.2 to 1.8 % higher methylation. The effect estimates were lower in 10 of the 15 CpG sites when comparing current to former smoking. One CpG site, cg05603985 (SKI), was found to be associated with expression of nearby CAD-related gene PRKCZ. CONCLUSIONS: Our study suggests an effect of tobacco smoking on DNA methylation of CAD-related genes and thus provides novel insights in the pathways that link tobacco smoking to risk of CAD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-015-0088-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4443552 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44435522015-05-27 Tobacco smoking is associated with methylation of genes related to coronary artery disease Steenaard, Rebecca V Ligthart, Symen Stolk, Lisette Peters, Marjolein J van Meurs, Joyce B Uitterlinden, Andre G Hofman, Albert Franco, Oscar H Dehghan, Abbas Clin Epigenetics Research BACKGROUND: Tobacco smoking, a risk factor for coronary artery disease (CAD), is known to modify DNA methylation. We hypothesized that tobacco smoking modifies methylation of the genes identified for CAD by genome-wide association study (GWAS). RESULTS: We selected genomic regions based on 150 single-nucleotide polymorphisms (SNPs) identified in the largest GWAS on CAD. We investigated the association between current smoking and the CpG sites within and near these CAD-related genes. Methylation was measured with the Illumina Human Methylation 450K array in whole blood of 724 Caucasian subjects from the Rotterdam Study, a Dutch population based cohort study. A total of 3669 CpG sites within 169 CAD-related genes were studied for association with current compared to never smoking. Fifteen CpG sites were significantly associated after correction for multiple testing (Bonferroni-corrected p value <1.4 × 10(−5)). These sites were located in the genes TERT, SARS, GNGT2, SMG6, SKI, TOM1L2, SIPA1, MRAS, CDKN1A, LRRC2, FES and RPH3A. In 12 sites, current smoking was associated with a 1.2 to 2.4 % lower methylation compared to never smoking; and in three sites, it was associated with a 1.2 to 1.8 % higher methylation. The effect estimates were lower in 10 of the 15 CpG sites when comparing current to former smoking. One CpG site, cg05603985 (SKI), was found to be associated with expression of nearby CAD-related gene PRKCZ. CONCLUSIONS: Our study suggests an effect of tobacco smoking on DNA methylation of CAD-related genes and thus provides novel insights in the pathways that link tobacco smoking to risk of CAD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-015-0088-y) contains supplementary material, which is available to authorized users. BioMed Central 2015-05-14 /pmc/articles/PMC4443552/ /pubmed/26015811 http://dx.doi.org/10.1186/s13148-015-0088-y Text en © Steenaard et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Steenaard, Rebecca V Ligthart, Symen Stolk, Lisette Peters, Marjolein J van Meurs, Joyce B Uitterlinden, Andre G Hofman, Albert Franco, Oscar H Dehghan, Abbas Tobacco smoking is associated with methylation of genes related to coronary artery disease |
title | Tobacco smoking is associated with methylation of genes related to coronary artery disease |
title_full | Tobacco smoking is associated with methylation of genes related to coronary artery disease |
title_fullStr | Tobacco smoking is associated with methylation of genes related to coronary artery disease |
title_full_unstemmed | Tobacco smoking is associated with methylation of genes related to coronary artery disease |
title_short | Tobacco smoking is associated with methylation of genes related to coronary artery disease |
title_sort | tobacco smoking is associated with methylation of genes related to coronary artery disease |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443552/ https://www.ncbi.nlm.nih.gov/pubmed/26015811 http://dx.doi.org/10.1186/s13148-015-0088-y |
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