Fluoride exposure and children's intelligence: Gene-environment interaction based on SNP-set, gene and pathway analysis, using a case-control design based on a cross-sectional study. (October 2021)

• Record Type: Journal Article
• Authors: Yu, Xingchen; Xia, Lu; Zhang, Shun; Zhou, Guoyu; Li, Yonggang; Liu, Hongliang; Hou, Changchun; Zhao, Qian; Dong, Lixin; Cui, Yushan; Zeng, Qiang; Wang, Aiguo; Liu, Li
• Is Part Of: Environment international. Volume 155(2021)
• Publication Date: 2021-10
• Subjects: Fluoride -- Intelligence loss -- Interaction -- SNP panel -- Pathway analysis; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2021.106681
• Languages: English
• ISSNs: 0160-4120

Abstract

Graphical abstract: Highlights: High intelligence was inversely correlated with water, urinary, hair and nail fluoride. Fluoride interacts with a SNP-set of rs3788319, rs1879417, rs57377675, rs11556505 and rs7187776 on intelligence. Fluoride interacts with mitochondrial function-related genes CLU and TOMM40 on intelligence. Multiple neurodevelopmental pathways related to metabolism may be involved in the fluoride-induced neurotoxicity. Abstract: Background: Excessive fluoride exposure has been associated with intelligence loss, but little is known about gene-fluoride interactions on intelligence at SNP-set, gene and pathway level. Objectives: Here we conducted a population-based study in Chinese school-aged children to estimate the associations of fluoride from internal and external exposures with intelligence as well as to explore the gene-fluoride interactions on intelligence at SNP-set, gene and neurodevelopmental pathway level. Methods: A total of 952 resident children aged 7 to 13 were included in the current study. The fluoride contents in drinking water, urine, hair and nail were measured using the ion-selective electrode method. LASSO Binomial regression was conducted to screen the intelligence-related SNP-set. The gene-fluoride interactions at gene and pathway levels were detected by the Adaptive Rank Truncated Product method. Results: The probability of high intelligence was inversely correlated with fluoride contents in water, urine, hair and nail (all P < 0.001). The SNP-set based on rs3788319, rs1879417, rs57377675, rs11556505 and rs7187776 was related to high intelligence ( P = 0.001) alone and by interaction with water, urinary and hair fluoride ( P = 0.030, 0.040, 0.010), separately. In gene level, CLU and TOMM40 interacted with hair fluoride (both P = 0.017) on intelligence. In pathway level, Alzheimer disease pathway, metabolic pathway, signal transduction pathway, sphingolipid signaling pathway and PI3K-AKT signaling pathway interacted with fluoride on intelligence in men. Conclusions: Our study suggests that fluoride is inversely associated with intelligence. Moreover, the interactions of fluoride with mitochondrial function-related SNP-set, genes and pathways may also be involved in high intelligence loss.