Erythrocyte magnesium concentrations and NIPA1/NIPA2 gene expression in children with autism spectrum disorder

Abstract

While genetic and environmental factors are involved in Autism Spectrum Disorder (ASD), the role of magnesium (Mg 2+ ) homeostasis remains a burgeoning field of interest. This cross-sectional study analyzed the association between erythrocyte Mg 2+ concentrations, clinical characteristics, and the expression of Mg 2+ transporter genes ( NIPA1 and NIPA2 ) in children with and without ASD. Intracellular Mg 2+ levels were determined, and relative gene expression was evaluated to detect molecular trends. The unadjusted analyses initially demonstrated lower erythrocyte Mg 2+ concentrations in children with ASD. However, this statistical association was completely attenuated after adjusting for clinical confounding variables, such as selective eating habits and pharmacotherapy. This indicates that the observed variations in Mg 2+ levels are influenced by these clinical covariates rather than constituting an intrinsic biological biomarker of autism. Concurrently, multivariable analysis adjusted associations with ASD status regarding NIPA1 and NIPA2 gene expression, highlighting complex metabolic and genetic trends that require cautious interpretation due to reference gene instability. In conclusion, these findings suggest that behavioral and pharmacological factors significantly alter traditional metabolic markers, emphasizing the need for multi-reference gene panels in future prospective neurodevelopmental research to ensure robust biological validation.