Low-to-moderate fluoride exposure, relative mitochondrial DNA levels, and dental fluorosis in Chinese children

The alteration of mitochondrial DNA (mtDNA) content contributes to many diseases, however, little is known about its effect on the prevalence of dental fluorosis (DF).We conducted a cross-sectional study to investigate the association of low-to-moderate fluoride exposure with relative mtDNA levels in relation to DF in children.We recruited 616 resident children, aged 7-13 years, randomly from low-to-moderate fluoride areas in Tianjin, China. We measured the fluoride concentrations in drinking water and urine using the national standardized ion selective electrode method, and determined the relative levels of mtDNA using a quantitative real-time polymerase chain reaction assay. The association among fluoride exposure, relative mtDNA levels, and the prevalence of DF were examined using multivariable linear and logistic regression models. We also performed stratified and mediation analyses.The relative mtDNA levels of participants in the DF group were significantly lower than in the non-DF group (0.95 ± 0.44 vs. 1.12 ± 0.45, P < 0.001). In the adjusted models, we found that a 1 mg/L increment in water fluoride concentration was associated with a 0.10-unit decrease in circulating relative mtDNA levels (95% CI: -0.14, -0.06) and a 2.85-fold increase (95% CI: 2.01, 3.92) in moderate DF prevalence. A 1 mg/L increment in urinary fluoride level was associated with a 0.12-unit decrease in circulating relative mtDNA levels (95% CI: -0.14, -0.09) and a 1.85-fold increase (95% CI: 1.39, 2.39) in moderate DF prevalence. Stratified analysis indicated a weaker positive association of DF prevalence with fluoride exposure, while a stronger inverse relationship with relative mtDNA levels in boys than in girls. Assuming causality, we estimated that circulating mtDNA levels mediated 13.0% (95% CI: 5.2, 28.7%) and 9.6% (95% CI: 4.7, 18.5%) of the estimated effect of a 1 mg/L increment in water fluoride and urinary fluoride on prevalence of moderate DF, respectively.Gender potentially modifies the associations of DF prevalence with relative mtDNA levels and low-to-moderate fluoride exposure. The reduced circulating mtDNA levels may partly mediate the elevated prevalence of moderate DF in children under such exposure.