Tobacco smoking is associated with methylation of genes related to coronary artery disease

Clinical Epigenetics

Abbas Dehghan³  Oscar H Franco³  Albert Hofman³  Andre G Uitterlinden²  Joyce B van Meurs⁴  Marjolein J Peters²  Lisette Stolk⁴  Symen Ligthart³  Rebecca V Steenaard¹ 

[1] Netherlands Institute for Health Sciences, Erasmus University Medical Centre, ‘s Gravendijkwal 230, Rotterdam, 3015 CE, The Netherlands;The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Einthovenweg 20, 2333 ZC Leiden/ ‘s Gravendijkwal 230, Rotterdam, 3015 CE, The Netherlands;Department of Epidemiology, Erasmus University Medical Centre, ‘s Gravendijkwal 230, Rotterdam, 3015 CE, The Netherlands;Department of Internal Medicine, Erasmus University Medical Centre, ‘s Gravendijkwal 230, Rotterdam, 3015 CE, The Netherlands

关键词: White blood cells;    Coronary artery disease;    Tobacco smoking;    mRNA expression;    DNA methylation;   

Others  :  1210204
DOI  :  10.1186/s13148-015-0088-y

 received in 2015-02-19, accepted in 2015-04-30,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Steenaard et al.; licensee BioMed Central.

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