Association of polymorphisms in the vitamin D receptor gene and serum 25-hydroxyvitamin D levels in children with autism spectrum disorder - May 2016
Gene, Available online 4 May 2016, doi:10.1016/j.gene.2016.05.004
Salih Coşkun a, , scoskun9 at gmail.com, Şeref Şimşek b, M.Akif Camkurt c, Abdullah Çim a, Sercan Bulut Çelik d
a Dicle University, Medical School, Department of Medical Genetics, Diyarbakır, Turkey
b Dicle University, Medical School, Department of Child Psychiatry, Diyarbakır, Turkey
c Afşin State Hospital, Psychiatry Department, Kahramanmaraş, Turkey
d Family health center, Batman, Turkey
- Autism rate in siblings reduced 4X by vitamin D: 5,000 IU during pregnancy, 1,000 IU to infants – Feb 2016
- Vitamin D Receptor category listing has
316 items along with related searches
Pages listed in BOTH the categories Autism and Genetics
Autism treated by Vitamin D: Dr. Cannell - video June 2013 includes many reasons why he believes Autism is related to Vitamin D
- Both have strong inheritance features – Vitamin D about 60%
- Both have gotten substantially worse in last 30 years
- Vitamin D is known to be involved in brain development
- All autistic children are VitD deficient, but not all children who are deficient are autistic: genes are involved
- When giving vitamin D to cure children of rickets “mental dullness” decreases as well
- Children with genes which give them too much (Williams Syndrome) have to reverse of autism – too sociable
- Mothers having lots of fish (and thus more vitamin D) give birth to kids with less autistic symptoms
- Both associated with weak bones
- Both worse around the age of weaning
- Autism is more common in rich families – more likely to apply sun screen and stay indoors
- Autism increases with drugs which lower levels of vitamin D
- Seizures are common with Autism - Vitamin D has been shown to reduce seizures
- Fewer autistic symptoms (such as sleep problems) during summer: when child gets more vitamin D from the sun
- Both worse with latitude
- Both vary with Ultraviolet light
- Both vary with time of year (more birth of autistics in March in Northern hemisphere)
- 2X more urban autism – less UVB in urban environments
- Both worse with pollution
- Both worse with increased clouds and rain
- Both worse with closely spaced pregnancies
- Autistics have abnormal immune response – similar to that of vitamin D deficiency
- Low levels of vitamin D in mother animals reduces brain function in offspring
- Vitamin deficient rat pups have similar brain abnormalities to that of human autistic children
- Autistic children get less vitamin D in their blood for the same amount of sun exposure
- The 4 males/1 female ratio - Note estrogen increases vitamin D in the brain (testosterone does not)
- Both worse in African Americans (A-A 2-3 increased autism rate)
- Both worse in Dark-skinned immigrants in Europe
- Note: All articles in Autism category
- 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.
Abbreviations: VDR, Vitamin D receptor gene; ASD, Autism Spectrum Disorder; 25(OH) D, 25-hydroxyvitamin D; HWE, Hardy–Weinberg equilibrium; SNP, Single nucleotide polymorphism; MS, Multiple sclerosis
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Vitamin D Receptor Gene Polymorphisms Associated with Childhood Autism
Brain Sci. 2017, 7(9), 115; Published: 9 September 2017 doi:10.3390/brainsci7090115 (registering DOI)
Anna Cieślińska 1, Elżbieta Kostyra 1, Barbara Chwała 2, Małgorzata Moszyńska-Dumara 3, Ewa Fiedorowicz 1, Małgorzata Teodorowicz 4 and Huub F.J. Savelkoul 4,* OrcID
1 Faculty of Biology and Biotechnology, University of Warmia and Mazury, 10-719 Olsztyn, Poland
2 Regional Children’s Hospital in Olsztyn, 10-719 Olsztyn, Poland
3 Center for Diagnosis, Treatment and Therapy of Autism at the Regional Children’s Hospital in Olsztyn, 10-719 Olsztyn, Poland
4 Cell Biology and Immunology Group, Wageningen University& Research, P.O. Box 338, 6700 AH Wageningen, The Netherlands
Background: Autism spectrum disorder (ASD) is a group of heterogeneous, behaviorally defined disorders whereby currently no biological markers are common to all affected individuals. A deregulated immune response may be contributing to the etiology of ASD. The active metabolite of vitamin D3 has an immunoregulatory role mediated by binding to the vitamin D receptor (VDR) in monocyte, macrophages, and lymphocytes. The effects of vitamin D and interaction with the VDR may be influenced by polymorphism in the VDR gene.
Methods: Genetic association of four different VDR polymorphisms (Apa-I, Bsm-I, Taq-I, Fok-I) associated with susceptibility to the development of autism in children was investigated.
Results: We uniquely found an association between the presence of the T allele at position Taq-I and presence of the a allele at position Apa-I of the VDR gene with decreased ASD incidence. There was also an association between female gender and the presence of the T allele. We found no statistical significant correlation between VDR single nucleotide polymorphisms (SNPs) and vitamin D3 concentration in serum of ASD children.
Conclusion: Genetic polymorphism in two SNP in VDR may be correlated with development of ASD symptoms by influencing functionality of vitamin D3 metabolism, while vitamin D3 levels were not significantly different between ASD and non-ASD children. View Full-Text