IndexVitamin DFunctions of vitamin DDevelopmental changes of the vitamin D receptor in ASDConclusionAutism spectrum disorders are disorders with multiple etiologies of genetic and non-genetic origins. Promising advances in ASD research in recent years have provided several important insights into the impact of vitamin D as a causal factor in ASD. Vitamin D receptor polymorphism plays an essential role in the development of several neuropsychiatric disorders including ASD. In this article, we reviewed all available relevant studies on vitamin D receptor polymorphism in autism spectrum disorder from PubMed, Google Scholar, Science direct, Cochrane Library using keywords and discarded irrelevant studies regardless of publication date. We found that several VDR variants, FokI, BsmI, and TaqI polymorphisms are related to ASD. Paternal VDR polymorphism may also be a causal factor of ASD in offspring. The relationship between FokI (ff) genotype polymorphism and increased serum 1,25(OH)D3 level in ASD patients is a very significant finding. However, there are many still unresolved questions that need to be answered. How you need to address the increased vitamin D level associated with ASD and what factors contribute to causing vitamin D receptor polymorphism. Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an Original Essay Autism spectrum disorder is attributed to a wide range of conditions represented by impaired social skills, repetitive behaviors, language, and nonverbal communications, as well as, unique strengths and differences. Autism spectrum disorder affects more than 1% of children in the United States. ASD is defined primarily by signs and symptoms nor by etiology. Only 10-35% of ASDs have a known major risk factor while in other cases the etiologies are mostly unknown. Based on the predominant symptom of children, there are several subgroups of ASD such as autism, Asperger syndrome, and pervasive developmental disorder not otherwise specified. Individuals with ASD have difficulty establishing relationships with others, expressing and understanding emotions, inability to act appropriately, which makes it difficult for them to live freely. Patients with autism are also vulnerable to behavioral and medical problems. There is evidence that abnormalities in inflammatory markers, autoantibodies against the brain, and glutathione subsets are present in patients with autism suggesting that ASD is a disease related to systemic inflammation, autoimmunity, and oxidative stress in our body. The prevalence of ASD has increased dramatically in recent years. It is now believed that there are some environmental risk factors and genetic causes that also play a role in ASD. Cannel's publication in 2008 revealed a hypothesis that a low level of vitamin D in fetal life and even in early childhood plays an important role in ASD. Animal studies show that vitamin D deficiency in fetal life has a tremendous effect on the neurological development of offspring, causing structural and functional changes in the brain and behavior. Vitamin D has an important role in neurotransmission, neuroprotection which defines the connection between several neuropsychiatric disorders in relation to vitamin D.Vitamin DVitamin D is a prohormone although classified as a vitamin. In general, food is a rare source of vitamin D, with the exception of fish liver oil and plants such as Solanumglaucophyllum. Vitamin D, which is a fat-soluble vitamin, is a collection of substances similar to the steroids ergocalciferol (D2) and cholecalciferol (D3). A significant source of vitamin D is through skin exposure to UVB rays. During sun exposure, 7-dihydroxycholesterol in the epidermis and dermis absorbs UVB and is converted into pre-vitamin D3. Through heat-induced isomerization, pre-vitamin D3 transforms into vitamin D3. sun exposure Figure #1: Pathway of vitamin D synthesis in the human body Action of vitamin D Pathways Vitamin D follows two genomic and non-genomic pathways of action. In the genomic pathway, vitamin D binds to VDR, a member of the steroid/thyroid transcription factor superfamily. After binding to vitamin D, they are phosphorylated in the fetal VDR; they then become heterodimerized with the retinoid X receptor which binds to the VDRE within the genome to influence gene transcription. A study of 2,200 genomic locations in the VDR confirmed that vitamin D is pleiotropic. In the non-genomic pathway, vitamin D binds to membrane-bound VDR or protein disulfide isomerase-associated protein 3 (PDIA3). Following the signal transduction pathway, Vit D causes the release of an intracellular influx of Ca2+ which leads to the activation of protein kinase which ultimately modifies the phosphorylation of cellular proteins. The study demonstrated that the non-genomic pathway of vitamin D action has an important role in cell proliferation and immune function. Both VDR and PDIA have been identified in the human brain. 3. Functions of Vitamin D Vitamin D is the primary hormone for regulating calcium and phosphorus. It also plays a role in bone formation, resorption, mineralization and maintenance of neuromuscular function. Rickets and osteomalacia are two well-known conditions caused by vitamin D deficiency, but many other conditions related to vitamin D deficiency are reported. 15 different types of cancer, osteoporosis, orthostatic hypotension, diabetes mellitus, hypertension have also been reported , hyperlipidemia, inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis related to vitamin D deficiency. Role of vitamin D in ADHD, development Vitamin D metabolite signaling has been detected in the human brain and appears to have steroid-like properties. Metabolites Vitamin D can easily cross the blood brain barrier. Cytochrome P450 enzymes regulating vitamin D synthesis found in the human fetal brain. CYP27B1 in the human fetal and adult brain. In the adult brain, CYP27B1 was present in neurons, glial cells of schizophrenia, expressed in the substantia nigra, supraoptic and paraventricular nuclei of the hypothalamus. The distribution of CYP2ZB1 in the adult brain demonstrates that the brain can synthesize the active metabolite 1,25(OH)2D3. Vitamin D plays a crucial role in pregnancy thanks to its primary role in the development of the fetal brain. Inadequate exposure to vitamin D causes several changes in the fetal brain that are responsible for adverse outcomes in brain function in later life. A study was conducted on BALB/c mice and demonstrated that maternal vitamin D deficiency caused neuroanatomical alterations and a revision of gene expression. In fetal mice, vitamin D deficiency caused suppression of neural FoxP2 and tyrosine hydroxylase especially in females. Fox P2 is an essential gene for the development of speech and language that causes dyspraxia, difficulties in expressive and receptive language, and this is the pathway that is hindered in some cases of ASD. FoxP2 knockout models showed delays in development, function.