Smoking-Related DNA Methylation is Differentially Associated with Cadmium Concentration in Blood

Abstract

Tobacco smoking, a risk factor for several human diseases, can lead to alterations in DNA methylation. Smoking is a key source of cadmium exposure; however, there are limited studies examining DNA methylation alterations following smoking-related cadmium exposure. To identify such cadmium exposure-related DNA methylation, we performed genome-wide DNA methylation profiling using DNA samples from 50 smokers and 50 non-smokers. We found that a total of 136 CpG sites (including 70 unique genes) were significantly differentially methylated in smokers as compared to that in non-smokers. The CpG site cg05575921 in the AHRR gene was hypomethylated (Δ ß > − 0.2) in smokers, which was in accordance with previous studies. The rs951295 (within RNA gene LOC105370802) and cg00587941 sites were under-methylated by > 15% in smokers, whereas cg11314779 (within CELF6) and cg02126896 were over-methylated by ≥ 15%. We analyzed the association between blood cadmium concentration and DNA methylation level for 50 smokers and 50 non-smokers. DNA methylation rates of 307 CpG sites (including 207 unique genes) were significantly correlated to blood cadmium concentration (linear regression P value < 0.001). The four significant loci (cg05575921 and cg23576855 in AHRR, cg03636183 in F2RL3, and cg21566642) were under-methylated by > 10% in smokers compared to that in non-smokers. In conclusion, our study demonstrated that DNA methylation levels of rs951295, cg00587941, cg11314779, and cg02126896 sites may be new putative indicators of smoking status. Furthermore, we showed that these four loci may be differentially methylated by cadmium exposure due to smoking.

Examining the association between adiposity and DNA methylation: A systematic review and meta‐analysis

“…Fifteen CpG sites have previously been associated with smoking. [88][89][90][91][92][93][94][95][96][97][98][99][100][101][102] This may represent a significant confounder in the BMI-methylation association in these sites. Of the EWAS examined in our meta-analysis, less than half included smoking as a covariate in the EWAS models.…”

“…As these sites were identified in BMI‐adjusted models in the previous EWAS, these also likely represent the upstream effects of diet and differential diet quality associated with obesity. Fifteen CpG sites have previously been associated with smoking 88–102 . This may represent a significant confounder in the BMI‐methylation association in these sites.…”

Association between DNA methylation and smoking in patients with chronic limb - threatening ischemia

“…Estos datos están en concordancia con estudios previos que demuestran una asociación del cg03636183 con el tabaquismo (20)(21)(22), así como con la carga de tabaco (21,22) y con el abandono del tabaco (22).…”

CELF Family Proteins in Cancer: Highlights on the RNA-Binding Protein/Noncoding RNA Regulatory Axis

“…Lastly, exposure to cadmium through smoking is implicated in the DNA methylation modifications of oncogenes, tumor suppressor genes, and genes related to inflammation, making it one of the important risk factors for cancer [122,123]. A recent study in 2020 showed that elevated cadmium concentrations in the blood are involved in the overmethylation of the cg11314779 site within the CELF6 gene, which is probably associated with its silencing [124,125]. CELF6 appears to play an essential role in tumor suppression via global post-transcriptional changes.…”