AHRR cg05575921 methylation in relation to smoking and PM2.5 exposure among Taiwanese men and women

Abstract

Background: 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. Methods: 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). Results: 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,

Epigenetics of single-site and multi-site atherosclerosis in African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA)

“…Similar to our findings, the association with cg05575921 in MESA remained significant after adjusting for self-reported smoking exposure, urinary cotinine, and other CVD risk factors, and remained significant in stratified analysis of former smokers and current smokers but not never smokers. Other studies have also reported evidence of cg05575921 differential methylation by air pollution in adults [ 62 ], by maternal smoking in neonates [ 63 , 64 ], and by smoking in atherosclerotic plaque specimens [ 65 ]. Similarly, cg09935388, located in the growth factor independent 1 transcriptional repressor gene ( GFI1 ) gene body region, has been found to be associated with smoking [ 32 , 66 , 67 ] and exposure to maternal smoking in fetuses [ 68 , 69 ].…”

The relationship of smoking to cg05575921 methylation in blood and saliva DNA samples from several studies

“…The second challenge to establishing a set point is variability in air quality. Studies from Taiwan have shown that air quality can have a small, but significant effect on cg05574921 levels 48 . However, the levels of air pollution in Taiwan are relatively low and fortunately, the level of PAH in the Midwestern United States are relatively low 49 .…”

Hypomethylation of AHRR (cg05575921) Is Related to Smoking Status in the Mexican Mestizo Population

“…As a result, increasing research proposes evaluating the methylation status in CpG sites related to smoking as a biomarker of smoking status [25,26,52,55,56,58,59]. Understanding the relationship between the epigenetic effects of smoking can increase our knowledge of the damage mechanisms that lead to chronic diseases related to tobacco smoking [14,23,[27][28][29][30][31]60,61].…”

“…The level of methylation of cg05575921 is associated with asthma development in infants born to smoking mothers [24], impaired lung function, COPD development and exacerbations [25,26], and carcinogenesis [22,23,[26][27][28][29][30][31].…”