Abstract
BACKGROUND: Imbalances in metal elements have been identified as a potential risk factor for autism spectrum disorder (ASD), and shortened telomere length (TL) is commonly observed in children with ASD. Metal elements may influence telomere homeostasis through oxidative stress, which could contribute to the pathogenesis of autism. However, studies examining the combined effects of metal elements on TL in children with ASD are limited. To fill the gaps in the current literature, this study aimed to investigate the relationship between six metallic elements: manganese (Mn), copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), and iron (Fe), and TL in the whole blood of children with ASD. METHODS: A total of 83 children with ASD and 95 typically developing children were recruited. TL was measured using digital PCR, while metal concentrations were assessed using inductively coupled plasma mass spectrometry (ICP-MS). Linear regression analysis was first conducted to explore the correlations between metal elements and TL in both groups. Additionally, Bayesian Kernel Machine Regression (BKMR) was used to further examine the combined effects and potential interactions of these metals on TL in the ASD group. RESULTS: In the ASD group, Ca was found to have a protective effect on TL (β = 0.07, 95% CI [0.01-0.13], P = 0.027). In contrast, Mg showed a protective effect on TL in the control group (β = 0.10, 95% CI [0.01-0.18], P = 0.027). The BKMR model revealed a significant positive combined effect of the metal mixtures on TL in the ASD group, with Ca having the largest individual effect (PIP = 0.45). Further analysis indicated that increases in Zn and Mn concentrations from the 25th to the 75th percentile were negatively correlated with TL, while higher concentrations of Cu, Ca, Mg, and Fe were positively associated with TL. No significant interactions among the metals were observed. CONCLUSIONS: This study suggests a potential link between metallic elements and TL in children with ASD, with Ca having the greatest effect. Our findings highlight the potential benefits of appropriate calcium supplementation as a protective strategy for lengthening telomeres in children with ASD, emphasizing the importance of early nutritional interventions to improve their overall health.