Chien-Yu Lin1, Hui-Ling Lee2, Yi-Ting Hwang3, Po-Chin Huang4, Chikang Wang5, Fung-Chang Sung6, Charlene Wu7, Ta-Chen Su8. 1. Department of Internal Medicine, En Chu Kong Hospital, New Taipei City, 237, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei City, 242, Taiwan; Department of Environmental Engineering and Health, Yuanpei University of Medical Technology, Hsinchu, 300, Taiwan. Electronic address: lin7010@mail2000.com.tw. 2. Department of Chemistry, Fu Jen Catholic University, New Taipei City, 242, Taiwan. 3. Department of Statistics, National Taipei University, New Taipei City, 237, Taiwan. 4. National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, 350, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404, Taiwan. 5. Department of Environmental Engineering and Health, Yuanpei University of Medical Technology, Hsinchu, 300, Taiwan. 6. Department of Health Services Administration, College of Public Health, China Medical University, Taichung, 404, Taiwan. 7. Global Health Program, National Taiwan University, College of Public Health, 10055, Taiwan. 8. Department of Environmental and Occupational Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan; Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan; Institute of Environmental and Occupational Health Sciences, College of Public Health, National Taiwan University, Taipei, 100, Taiwan. Electronic address: tachensu@gmail.com.
Abstract
PURPOSE: Lead (Pb) or cadmium (Cd) exposure has been linked to atherosclerosis. Co-exposure of these two heavy metals often occurs in humans. Recent evidence has indicated a crucial role of DNA methylation in atherosclerosis, while Pb or Cd exposure has also been shown to alter DNA methylation. However, it is still unknown whether DNA methylation plays a role in the pathological mechanism of these two heavy metals in atherosclerosis. APPROACH AND RESULTS: We enrolled 738 participants (12-30 years) to investigate the association among concentrations of urine Pb or Cd, the 5mdC/dG value (a global DNA methylation marker) and the carotid intima-media thickness (CIMT). When each heavy metal was modeled separately, the results showed urine Pb and Cd concentrations were positively associated with the 5mdC/dG value and CIMT, respectively. When the two heavy metals were analyzed in the same model, urinary Pb concentrations were positively associated with the 5mdC/dG value and CIMT, while urinary Cd concentrations were only positively associated with the CIMT. When Pb and Cd are simultaneously considered in the same logistic regression model, the odds ratios (OR) of thicker CIMT (greater than 75th percentile) with one unit increase in ln-Pb level was 1.67 (95% C.I. = 1.17-2.46, P = 0.005) when levels of 5mdC/dG were above 50th percentile, which is higher than 5mdC/dG bellow the 50th percentile (OR = 1.50 (95% C.I. = 0.96-2.35), P = 0.076). In structural equation model (SEM), Pb or Cd levels are directly associated with CIMT. Moreover, Pb or Cd had an indirect association with CIMT through the 5mdC/dG. When we considered Pb and Cd together, Pb levels had a direct association with CIMT and an indirect association with CIMT through the 5mdC/dG value, while Cd only had a direct association with CIMT. CONCLUSIONS: Our findings imply that Pb and Cd exposure might be associated with subclinical atherosclerosis, and global DNA methylation might mediate Pb-associated subclinical atherosclerosis in this young population. Future effort is necessary to elucidate the causal relationship.
PURPOSE: Lead (Pb) or cadmium (Cd) exposure has been linked to atherosclerosis. Co-exposure of these two heavy metals often occurs in humans. Recent evidence has indicated a crucial role of DNA methylation in atherosclerosis, while Pb or Cd exposure has also been shown to alter DNA methylation. However, it is still unknown whether DNA methylation plays a role in the pathological mechanism of these two heavy metals in atherosclerosis. APPROACH AND RESULTS: We enrolled 738 participants (12-30 years) to investigate the association among concentrations of urine Pb or Cd, the 5mdC/dG value (a global DNA methylation marker) and the carotid intima-media thickness (CIMT). When each heavy metal was modeled separately, the results showed urine Pb and Cd concentrations were positively associated with the 5mdC/dG value and CIMT, respectively. When the two heavy metals were analyzed in the same model, urinary Pb concentrations were positively associated with the 5mdC/dG value and CIMT, while urinary Cd concentrations were only positively associated with the CIMT. When Pb and Cd are simultaneously considered in the same logistic regression model, the odds ratios (OR) of thicker CIMT (greater than 75th percentile) with one unit increase in ln-Pb level was 1.67 (95% C.I. = 1.17-2.46, P = 0.005) when levels of 5mdC/dG were above 50th percentile, which is higher than 5mdC/dG bellow the 50th percentile (OR = 1.50 (95% C.I. = 0.96-2.35), P = 0.076). In structural equation model (SEM), Pb or Cd levels are directly associated with CIMT. Moreover, Pb or Cd had an indirect association with CIMT through the 5mdC/dG. When we considered Pb and Cd together, Pb levels had a direct association with CIMT and an indirect association with CIMT through the 5mdC/dG value, while Cd only had a direct association with CIMT. CONCLUSIONS: Our findings imply that Pb and Cd exposure might be associated with subclinical atherosclerosis, and global DNA methylation might mediate Pb-associated subclinical atherosclerosis in this young population. Future effort is necessary to elucidate the causal relationship.
Authors: Airton C Martins; Ana Carolina B Almeida Lopes; Mariana R Urbano; Maria de Fatima H Carvalho; Ana Maria R Silva; Alexey A Tinkov; Michael Aschner; Arthur E Mesas; Ellen K Silbergeld; Monica M B Paoliello Journal: Ecotoxicol Environ Saf Date: 2020-11-20 Impact factor: 6.291