Association of polymorphisms in the vitamin D receptor gene and serum 25-hydroxyvitamin D levels in children with autism spectrum disorder

• There was significantly association between TaqI, BsmI and FokI polymorphisms and ASD susceptibility.
• The haplotype GTTT was found to confer 2.32-fold risk for ASD compared to controls.
• We found significantly higher serum 25(OH)D levels in ASD patients than controls.
• We showed an association between FokI polymorphism and serum 25(OH)D levels in ASD patients.

Vitamin D is implicated in several aspects of human physiology, and polymorphisms in the vitamin D receptor gene (VDR) are associated with a variety of neuropsychiatric disorders. The aims of this study are to determine whether VDR polymorphisms are associated with autism spectrum disorder (ASD), to examine serum 25-hydroxyvitamin D (25(OH)D) levels in ASD, and to explore whether VDR polymorphisms influence serum 25(OH)D levels. We investigated 480 subjects (237 children with ASD and 243 healthy controls) for the following VDR polymorphisms: TaqI, BsmI, FokI, ApaI, and Cdx2.Within the same samples, 25(OH)D levels were available only for 85 patients and 82 controls. The Cdx-2 variation was shown to deviate from Hardy–Weinberg equilibrium in the controls and was therefore excluded from the study. We found that the frequency of rare FokI TT, TaqI CC, and BsmI AA genotypes differed significantly between children with ASD and the controls (p = 0.042, p = 0.016, p = 0.038, respectively). After correction for multiple testing, only the TaqI CC genotype remained significant. Further analysis using a recessive model showed that rare genotypes of these polymorphisms were significantly higher in patients compared to controls (p = 0.045, p = 0.005 and p = 0.031, respectively). However, no significant association was found between ApaI and ASD. We found serum 25(OH)D levels to be significantly higher in children with ASD (p < 0.001) and that the FokI polymorphism had an effect on serum 25(OH)D levels in children with ASD (p = 0.041). Additionally, we found the haplotype GTTT (BsmI/TaqI/FokI/ApaI) conferred an increased risk for developing ASD (p = 0.022; odds ratio [95% confidence interval] = 2.322 [1.105–4.879]). This is the first clinical study evaluating the association between serum 25(OH)D levels and VDR polymorphisms in children with ASD. Our results demonstrated a significant association between TaqI, BsmI, and FokI polymorphisms and ASD and showed for the first time that FokI polymorphisms and haplotype GTTT (BsmI/TaqI/FokI/ApaI) are associated with an increased risk of ASD. Our findings support the hypothesis that 25(OH)D is involved in the pathophysiology of autism and that serum 25(OH)D levels may be affected by FokI polymorphisms in children with ASD. Our results should be considered as preliminary and needs confirmation by future studies.