Global DNA methylation and the association between metal exposure and chronic kidney disease

Frontiers in Public Health

Public Health

Hui-Ling Lee¹  Horng-Sheng Shiue²  Sheng-Lun Hsu³  Ying-Chin Lin⁴  Yu-Mei Hsueh⁵  Wei-Jen Chen⁶  Ya-Li Huang⁷  Hsi-Hsien Chen⁸ 

[1] Department of Chemistry, Fu Jen Catholic University, New Taipei City, Taiwan;Department of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan;Department of Family Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;Department of Family Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;Department of Geriatric Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;Department of Family Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;Department of Medicine, Section of Epidemiology and Population Sciences, Baylor College of Medicine, Houston, TX, United States;Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan;

关键词: 5-methyl-2-deoxycytidine;    arsenic;    cadmium;    lead;    selenium;    chronic kidney disease;   

DOI  :  10.3389/fpubh.2023.1104692

 received in 2022-11-21, accepted in 2023-05-08,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionPrior studies indicate that exposure to metals may alter DNA methylation. Evidence also shows that global DNA methylation is associated with chronic kidney disease (CKD). This study aimed to examine the association between CKD and 5-methyl-2-deoxycytidine (5mdC, %), a marker of global DNA methylation, and to evaluate the interaction between metal exposures and 5mdC (%) on CKD. We also explored the mediation effect of 5mdC (%) on the association between metal exposures and renal function (i.e., estimated glomerular filtration rate, eGFR).MethodsA total of 218 CKD patients and 422 controls were recruited in this case–control study. 5mdC (%), concentrations of blood lead and cadmium, plasma selenium, and total urinary arsenic were measured. CKD cases were clinically defined among patients with eGFR <60 mL/min/1.73 m2 for at least 3 months and without hemodialysis. Odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression models to examine the association between metal exposures, 5mdC (%), and CKD, adjusted for confounders. Multivariable linear regression models were used to examine associations between metal exposures, 5mdC (%), and eGFR.Results and DiscussionCKD cases compared to controls had 6.06-fold (95% CI: 3.11–11.81) higher odds of having high blood cadmium and high 5mdC (%) levels. A positive interaction on an additive scale was identified between blood cadmium and 5mdC (%) on CKD. Cases compared to controls had 4.73-fold (95% CI: 2.65–8.45) higher odds of having low plasma selenium and high 5mdC (%) levels; and a significant multiplicative interaction between plasma selenium and 5mdC (%) on CKD was observed. In addition, we found that blood lead and cadmium concentrations were positively associated, while plasma selenium concentrations were inversely associated, with 5mdC (%). The associations of blood lead and plasma selenium with eGFR were partially mediated by 5mdC (%). Our results suggest that 5mdC (%) may interact with plasma selenium and blood cadmium to influence the risk of CKD. The 5mdC (%) also potentially mediates the associations between exposure to metals and renal function.

【 授权许可】

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Copyright © 2023 Hsueh, Chen, Lee, Huang, Shiue, Hsu, Chen and Lin.