AHRR cg05575921 methylation in relation to smoking and PM_2.5 exposure among Taiwanese men and women

Polycyclic aromatic hydrocarbon (PAH)-rich substances like cigarette smoke and PM_2.5 induce aryl hydrocarbon receptor (AHR)-mediated aryl hydrocarbon receptor repressor (AHRR) methylation. AHRR cg05575921 and coagulation factor II (thrombin) receptor-like 3 (F2RL3) cg03636183 methylation patterns are well-established biomarkers for smoking. Even though AHRR cg05575921 methylation has recently been associated with PM_2.5, the interaction between smoking and PM_2.5 on AHRR methylation is yet to be fully explored. We evaluated AHRR and F2RL3 CpG sites to identify potential significant markers in relation to PM_2.5 and smoking in Taiwanese adults.

DNA methylation and smoking data of 948 participants aged 30-70 years were obtained from the Taiwan Biobank Database (2008-2015), while PM_2.5 data were obtained from the Air Quality Monitoring Database (2006-2011).

Smoking and PM_2.5 were independently associated with hypomethylation (lower levels) of AHRR cg05575921, AHRR cg23576855, F2RL3 cg03636183, and F2LR3 cg21911711 after multiple-comparison correction (Bonferroni P < 0.00028409). Cg05575921 was the most hypomethylated AHRR CpG site, while cg03636183 was the most hypomethylated F2RL3 CpG site. Overall, cg05575921 was the most hypomethylated CpG site: β = - 0.03909, P < 0.0001; - 0.17536, P < 0.0001 for former and current smoking, respectively (P-trend_smoking < 0.0001) and - 0.00141, P < 0.0001 for PM_2.5. After adjusting for F2RL3 cg03636183, smoking and PM_2.5 remained significantly associated with cg05575921 hypomethylation: β - 0.02221, P < 0.0001; - 0.11578, P < 0.0001 for former and current smoking, respectively (P-trend_smoking < 0.0001) and - 0.0070, P = 0.0120 for PM_2.5. After stratification by sex, smoking and PM_2.5 remained associated (P < 0.05) with cg05575921 hypomethylation in both men (β = - 0.04274, - 0.17700, and - 0.00163 for former smoking, current smoking, and PM_2.5, respectively) and women (β = - 0.01937, - 0.17255, and - 0.00105 for former smoking, current smoking, and PM_2.5, respectively). After stratification by residential area, former and current smoking remained associated (P < 0.05) with cg05575921 hypomethylation: β = - 0.03918 and - 0.17536, respectively (P-trend_smoking < 0.0001). Living in the central and southern areas was also associated (P < 0.05) with cg05575921 hypomethylation: β = - 0.01356 and - 0.01970, respectively (P-trend_area < 0.0001).

Smoking and PM_2.5 were independently associated with hypomethylation of cg05575921, cg23576855, cg03636183, and cg21911711. The most hypomethylated CpG site was cg05575921 and its association with smoking and PM_2.5 was dose-dependent.