Associations among global long interspersed nuclear element-1 DNA methylation, metal exposure, and chronic kidney disease

Yu-Mei Hsueh; Mei-Chieh Chen; Ying-Chin Lin; Chih-Yin Wu; Horng-Sheng Shiue; Sheng-Lun Hsu; Hsi-Hsien Chen; Ya-Li Huang

doi:10.1007/s00204-024-03780-9

Associations among global long interspersed nuclear element-1 DNA methylation, metal exposure, and chronic kidney disease

Arch Toxicol. 2024 May 16. doi: 10.1007/s00204-024-03780-9. Online ahead of print.

Authors

Yu-Mei Hsueh^{1

2}, Mei-Chieh Chen^{3

4}, Ying-Chin Lin^{1

5

6}, Chih-Yin Wu^{1

5}, Horng-Sheng Shiue⁷, Sheng-Lun Hsu¹, Hsi-Hsien Chen^{8

9}, Ya-Li Huang¹⁰

Affiliations

¹ Department of Family Medicine, Wanfang Hospital, Taipei Medical University, Taipei City, Taiwan.
² Department of Public Health, School of Medicine, College of Medicine, Zhonghe District, Taipei Medical University, No.301, Yuantong Road, New Taipei City, Taiwan.
³ Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan.
⁴ Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei City, Taiwan.
⁵ Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan.
⁶ Department of Geriatric Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan.
⁷ Department of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.
⁸ Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan.
⁹ Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei City, Taiwan.
¹⁰ Department of Public Health, School of Medicine, College of Medicine, Zhonghe District, Taipei Medical University, No.301, Yuantong Road, New Taipei City, Taiwan. ylhuang@tmu.edu.tw.

PMID: 38753188
DOI: 10.1007/s00204-024-03780-9

Abstract

Long interspersed nuclear element-1 (LINE-1) methylation serves as an indicator of global DNA methylation. This study explored the correlation between LINE-1 methylation and chronic kidney disease (CKD). We also evaluated whether LINE-1 methylation could modify the association between CKD and metal exposure. A total of 213 patients with clinically defined CKD, without hemodialysis and 416 age and sex matched controls were recruited. Levels of LINE-1 methylation, total urinary arsenic, blood lead, blood cadmium, and plasma selenium were assessed. The results reveal a positive association between LINE-1 methylation and CKD, with an odds ratio (OR) of 5.30 (95% confidence interval: 2.81 to 9.99). Total urinary arsenic and blood cadmium concentrations were positively related with LINE-1 methylation. This study was the first to observe that low plasma selenium, high blood cadmium, and high blood lead levels significantly and additively interact with increased LINE-1 methylation to increase the OR of CKD. Additionally, high LINE-1 methylation interacted multiplicatively with low plasma selenium to increase the OR of CKD (p < 0.001). This study highlighted the significant association between LINE-1 hypermethylation and CKD. Furthermore, the results demonstrate that LINE-1 methylation can interact with high blood cadmium or low plasma selenium to affect CKD risk.

Keywords: Cadmium; Chronic kidney disease; Lead; Long interspersed nuclear element-1 methylation; Selenium.

Abstract

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