Individual and joint associations of exposure to per- and polyfluoroalkyl substances with children's mitochondrial DNA copy number, and modified by estimated glomerular filtration rate

Biao Zhang; Jie Wang; Yuanyuan Zhang; Miao Liu; Xiaomin Zhang

doi:10.1016/j.envres.2024.120598

Individual and joint associations of exposure to per- and polyfluoroalkyl substances with children's mitochondrial DNA copy number, and modified by estimated glomerular filtration rate

Environ Res. 2024 Dec 10:266:120598. doi: 10.1016/j.envres.2024.120598. Online ahead of print.

Authors

Biao Zhang¹, Jie Wang¹, Yuanyuan Zhang¹, Miao Liu², Xiaomin Zhang³

Affiliations

¹ Department of Occupational and Environmental Health, Ministry of Education Key Laboratory of Environment and Health, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
² Department of Epidemiology, School of Public Health (Shenzhen), Sun Yat-Sen University, Shenzhen, Guangdong, China. Electronic address: [email protected].
³ Department of Occupational and Environmental Health, Ministry of Education Key Laboratory of Environment and Health, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: [email protected].

PMID: 39667485
DOI: 10.1016/j.envres.2024.120598

Abstract

Background: The association between per- and polyfluoroalkyl substances (PFAS) and mitochondrial DNA copy number (mtDNAcn) in children, and the potential impact of estimated glomerular filtration rate (eGFR) on this association, remains unclear.

Methods: We conducted a panel study with up to 3 surveys over 3 seasons in Weinan and Guangzhou, China. A total of 284 children aged 4-12 years were available, with 742 measurements of 11 PFAS and mtDNAcn. Linear mixed-effect (LME), quantile g-computation (qgcomp), weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models were used to investigate the associations of individuals and a mixture of PFAS with mtDNAcn, and the modifying effect of eGFR on these associations.

Results: Legacy PFAS, including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorooctane sulfonate (PFOS) and emerging PFAS, 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), were significantly associated with decreased mtDNAcn in a linear dose-response manner (FDR <0.05). The multiple PFAS model showed each doubling increase in PFOA related to a 6.36% (95%CI: -10.22%, -2.34%) decrement in mtDNAcn. Meanwhile, the PFAS mixture was dose-responsive related to decreased mtDNAcn, with PFOA being the largest contributor, followed by PFUnDA and PFNA. Notably, eGFR modified the inverse association between PFOA and mtDNAcn (P-int = 0.039), with a more pronounced decrement in children with an eGFR below the 20^th value (101.71 mL/min/1.73m²). In addition, age significantly modified the relationship between PFOA and decreased mtDNAcn (P-int = 0.028), with a stronger association in those aged 7 years or older.

Conclusion: Both individual and the mixture of legacy and emerging PFAS exposure were associated with decreased mtDNAcn in children, with PFOA as the main contributor and modification of eGFR.

Keywords: Children; Panel study; Per and polyfluoroalkyl substances mixture; eGFR; mtDNAcn.