DNA Methylation of the Aryl Hydrocarbon Receptor Repressor Associations with Cigarette Smoking and Subclinical Atherosclerosis

摘要: Background— Tobacco smoke contains numerous agonists of the aryl hydrocarbon receptor (AhR) pathway, and activation AhR pathway was shown to promote atherosclerosis in mice. Intriguingly, cigarette smoking is most strongly robustly associated with DNA modifications an gene, repressor ( AHRR ). We hypothesized that altered methylation monocytes, a cell type sensitive involved atherogenesis, may be part biological link between atherosclerosis. Methods Results— profiles monocytes (542 CpG sites±150 kb , using Illumina 450K array) were integrated habits ultrasound-measured carotid plaque scores from 1256 participants Multi-Ethnic Study Atherosclerosis (MESA). Methylation cg05575921 significantly P =6.1×10−134) status (current versus never). Novel associations =3.1×10−10) identified, which remained significant current former smokers even after adjusting for self-reported habits, urinary cotinine, well-known cardiovascular disease risk factors. This association replicated independent cohort hepatic (n=141). Functionally, located predicted gene expression regulatory element (enhancer) had correlated mRNA =1.4×10−17) obtained RNA sequencing conducted on subset (n=373) samples. Conclusions— These findings suggest functionally related represents potential biomarker subclinical smokers.