A DNA Methylation Marker, cg05575921 (AHRR), Outperforms Self-Reported Smoking Exposure for Its Association With Cardiovascular Disease Prevalence

Abstract

Background: The differential DNA methylation (DNAm) of the CpG site cg05575921, within the gene body of AHRR, has been shown to be a robust indicator of tobacco smoking exposure. This study aimed to determine if cg05575921 at AHRR DNAm had a clinically relevant association with prevalent cardiovascular disease (CVD) and compare its predictive performance with self-reported smoking assessments. Methods: Whole blood cg05575921 (AHRR) DNAm was assessed using a simple droplet digital PCR assay in a cohort of 2784 elderly individuals. DNAm values were used to impute smoking status and its independent association with prevalent CVD. Results: Consistent with previous reports, cg05575921 (AHRR) had significant, sensitive, and specific associations with self-reported smoking status (SRSS: never, ex-, current. <0.0001 between groups). This DNAm marker was also associated with the length of smoking cessation in ex-smokers (rho 0.55, p 21 years, ex-smoker quit <21 years, and current smoker), remained significantly associated with CVD after covariant adjustment, which included SRSS (OR 2.5, 3.1, and 6.0, p