Vitamin D is endowed with a number of biological properties, including down‐regulation of inflammation, and might contribute to the pathogenesis of autism spectrum disorders (ASD). Vitamin D binds to the vitamin D Receptor (VDR); the biological activity of the ensuing complex depends on VDR FokI, BsmI, ApaI, and TaqI gene polymorphisms. We evaluated such Single Nucletoide Polymorphismsm (SNPs) in a cohort of 100 Italian families with ASD children. FokI genotype distribution was skewed in ASD children compared with their healthy sibs (P_c = 0.03 2 df) and to a group of 170 Italian healthy women (HC) (P_c = 0.04 2 df). FokI genotype and allelic distribution skewing were also observed in mothers of ASD children compared to HC (P_c = 0.04 2 df). Both Transmission Disequilibrium Test for single loci and haplotype analysis distribution revealed a major FokI (C) allele‐mediated protective effect, which was more frequently transmitted (73%) than not transmitted to healthy sibs (P = 0.02). A protective FokI‐, BsmI‐, ApaI‐, and TaqI (CCAG) haplotype was more frequently carried by healthy sibs than by ASD children (P = 1 × 10⁻⁴; OR: 0.1, 95% CI: 0.03–0.4) too. Finally, a strong gene‐dose association of FokI (T) allele with both higher Childhood Autism Rating Scale score (P_c = 0.01) and, particularly, with hyperactivity behavior (P_c = 0.006) emerged in ASD children. Because the protein produced by the FokI (T) allele is transcriptionally less active than that produced by the FokI (C) allele, the reduced biological activity of the vitamin D/VDR complex prevalent in ASD could favor ASD‐ and maternal immune activation‐ associated inflammation. Vitamin D supplementation might be useful in preventative and rehabilitation protocols for ASD. Autism Res 2020, 13: 680–690. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

中文翻译：

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与自闭症谱系障碍相关的维生素D受体多态性。

维生素D具有多种生物学特性，包括炎症的下调，并且可能导致自闭症谱系障碍（ASD）的发病机理。维生素D与维生素D受体（VDR）结合；随后的复合物的生物学活性取决于VDR FokI，BsmI，ApaI和TaqI基因多态性。我们在一个100个带有ASD儿童的意大利家庭中评估了这种单核苷酸多态性（SNP）。的FokⅠ基因型分布在ASD儿童扭曲他们的健康同胞（相比P _{c ^} = 0.03 2 DF）和一组意大利170名健康妇女（HC）的（P _ç= 0.04 2 df）。与HC相比，在ASD儿童的母亲中也观察到了FokI基因型和等位基因分布偏斜（P _c = 0.04 2 df）。单个基因座的传播不平衡测试和单倍型分析分布均显示出主要的FokI（C）等位基因介导的保护作用，其传播频率（73％）比不传播至健康同胞（P = 0.02）。保护性FokI‐，BsmI‐，ApaI‐和TaqI（CCAG）单倍型由健康同胞比ASD儿童携带（P = 1×10⁻⁴ ; 或：0.1，95％CI：0.03-0.4）。最后，在ASD儿童中，FokI（T）等位基因与儿童自闭症评分量表评分较高（P _c = 0.01），特别是与多动行为（P _c = 0.006）密切相关。由于FokI（T）等位基因产生的蛋白质的转录活性低于FokI（C）等位基因产生的蛋白质，因此ASD中普遍存在的维生素D / VDR复合物的生物活性降低可能有利于ASD和母体免疫激活相关炎。补充维生素D可能有助于ASD的预防和康复方案。自闭症研究2020，13：680–690。©2020国际自闭症研究协会，Wiley Periodicals，Inc.。