Epigenetic Changes in Immune Response and Oncogenesis Related Genes Caused by Heavy Metal Long-Term Exposure

Our study investigated methylation changes in CpG islands located in immune response and oncogenesis related genes in humans induced by long-term environmental heavy metal exposure. We assessed the methylation levels of 654 CpG sites located on NFKB1, CDKN2A, ESR1, APOA5 and IGF2/H19 genes by targeted bisulfite sequencing (target enrichment by 48.48 Access Array Integrated Fluidic Circuit (Fluidigm, USA) in a cohort of 40 subjects living near a metal mining area (the Kapan mining region, Armenia) and 40 unexposed subjects. We performed linear regression on our data to find differentially methylated positions with adjustment for gender, age, BMI class, smoking, and plasma concentrations of 21 essential and non-essential metals detected by ICP-MS. Our study showed hypomethylation of five CpG sites in the NFKB1 promoter region in the exposed group. According to our findings, the methylation changes of CpG sites in NFKB1, CDKN2A, IGF2 and ESR1 genes are associated with multiple and specific metal exposures. Targeted bisulfite sequencing data obtained for 80 subjects who participated in this study are available through dbGaP. The tables contain information about age, sex, BMI, smoking and exposure status, as well as race and ethnicity of the study participants. ]]>
Inclusion Criteria: All subjects were of Armenian descent and had lived their entire lives in the respective location. All individuals recruited in study were healthy by self-report. Exposed subjects were selected based on the distance to the mine as well as reports on heavy metal levels in the habitation area. People, who are living near the mining region and regularly consume vegetables, fruits, and dairy with trace elements concentrations exceeding the maximum acceptable levels were recruited in a metal-exposed group. People, living in Yerevan city, Armenia, were recruited in the unexposed group since there is no mining activity around the city. Exclusion Criteria: Medical history of chronic diseases The use of mineral supplements Excessive alcohol consumption The presence of metal implants Vegetarianism and other specific eating habits Surgery or exposure to radiation or any chemicals at least a month before sampling Pregnancy]]>