Impact of gene polymorphisms involved in the vitamin D metabolic pathway on the susceptibility to and severity of autism spectrum disorder

Abstract

This study explores the association between genetic variations in the vitamin D pathway and autism spectrum disorder (ASD) susceptibility and severity in Thai children. A total of 276 participants, including 169 children with ASD and 107 healthy controls, were recruited. Genotyping of vitamin D pathway genes ( CYP2R1 , CYP27B1 , GC , and VDR ) was conducted using TaqMan-based real-time PCR, while serum vitamin D levels were measured by chemiluminescence immunoassay. ASD severity was assessed via the Childhood Autism Rating Scale, 2nd Edition. Results reveal that the VDR gene (ApaI) rs7975232 is linked to a reduced ASD risk. In contrast, the GC gene rs7041 (A > C) polymorphism shows a significant association with increased ASD risk and severity, particularly in individuals with both the GC gene polymorphism and vitamin D insufficiency. Additionally, there was a higher prevalence of the GC1s isoform and GC1s-GC1s haplotype in children with ASD, associated with ASD severity. This study identified that individuals possessing GC rs7041 C alleles and the GC1s genotype (rs7041 C /rs4588 G ) exhibit an increased susceptibility to and more severity of ASD. Further studies with larger cohorts are essential to fully understand these genetic polymorphisms’ roles. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-79994-9.