Vitamin D Receptor Gene Polymorphisms Associated with Childhood Autism

Overview

Journal Brain Sci

Publisher MDPI

Date 2017 Sep 12

PMID 28891930

Citations 20

Authors

Anna Cieslinska

Elzbieta Kostyra

Barbara Chwala

Malgorzata Moszynska-Dumara

Ewa Fiedorowicz

Malgorzata Teodorowicz

Huub F J Savelkoul

Affiliations

Soon will be listed here.

Abstract

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 allele at position Taq-I and presence of the 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 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.

Citing Articles

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

Saechua C, Sarachana T, Chonchaiya W, Trairatvorakul P, Yuwattana W, Poolcharoen C Sci Rep. 2024; 14(1):28333.

PMID: 39550459 PMC: 11569182. DOI: 10.1038/s41598-024-79994-9.

Genetic susceptibility of vitamin D receptor gene polymorphisms on autosomal recessive primary microcephaly patients in Pakistani population: a case-control and in-silico study.

Aslam K, Anjum I, Aslam K, Haq R, Bashir R Mol Biol Rep. 2023; 50(10):8049-8059.

PMID: 37541996 DOI: 10.1007/s11033-023-08681-1.

Comprehensive Intervention and Effect of Martial Arts Routines on Children with Autism.

Li L, Li H, Zhao Z, Xu S J Environ Public Health. 2022; 2022:9350841.

PMID: 36089974 PMC: 9451956. DOI: 10.1155/2022/9350841.

Vitamin D receptor gene variants and serum vitamin D in childhood autism spectrum disorder.

Zhang Z, Liu J, Jiang G, Yu H Mol Biol Rep. 2022; 49(10):9481-9488.

PMID: 35953654 DOI: 10.1007/s11033-022-07829-9.

Vitamin D: A Potential Mitigation Tool for the Endemic Stage of the COVID-19 Pandemic?.

Noriega D, Savelkoul H Front Public Health. 2022; 10:888168.

PMID: 35757617 PMC: 9226430. DOI: 10.3389/fpubh.2022.888168.

References

Humble M, Gustafsson S, Bejerot S . Low serum levels of 25-hydroxyvitamin D (25-OHD) among psychiatric out-patients in Sweden: relations with season, age, ethnic origin and psychiatric diagnosis. J Steroid Biochem Mol Biol. 2010; 121(1-2):467-70. DOI: 10.1016/j.jsbmb.2010.03.013. View

Eyles D, Burne T, McGrath J . Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front Neuroendocrinol. 2012; 34(1):47-64. DOI: 10.1016/j.yfrne.2012.07.001. View

Saadi A, Gao G, Li H, Wei C, Gong Y, Liu Q . Association study between vitamin D receptor gene polymorphisms and asthma in the Chinese Han population: a case-control study. BMC Med Genet. 2009; 10:71. PMC: 2720948. DOI: 10.1186/1471-2350-10-71. View

Giulivi C, Zhang Y, Omanska-Klusek A, Ross-Inta C, Wong S, Hertz-Picciotto I . Mitochondrial dysfunction in autism. JAMA. 2010; 304(21):2389-96. PMC: 3915058. DOI: 10.1001/jama.2010.1706. View

Bikle D . Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol. 2014; 21(3):319-29. PMC: 3968073. DOI: 10.1016/j.chembiol.2013.12.016. View

Holick M . Vitamin D deficiency. N Engl J Med. 2007; 357(3):266-81. DOI: 10.1056/NEJMra070553. View

Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G . Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects. Physiol Rev. 2015; 96(1):365-408. PMC: 4839493. DOI: 10.1152/physrev.00014.2015. View

Holick M . Photosynthesis of vitamin D in the skin: effect of environmental and life-style variables. Fed Proc. 1987; 46(5):1876-82. View

Cannell J . Autism and vitamin D. Med Hypotheses. 2007; 70(4):750-9. DOI: 10.1016/j.mehy.2007.08.016. View

10.

Kocovska E, Fernell E, Billstedt E, Minnis H, Gillberg C . Vitamin D and autism: clinical review. Res Dev Disabil. 2012; 33(5):1541-50. DOI: 10.1016/j.ridd.2012.02.015. View

11.

Buie T . The relationship of autism and gluten. Clin Ther. 2013; 35(5):578-83. DOI: 10.1016/j.clinthera.2013.04.011. View

12.

Sayeed I, Stein D . Progesterone as a neuroprotective factor in traumatic and ischemic brain injury. Prog Brain Res. 2009; 175:219-37. DOI: 10.1016/S0079-6123(09)17515-5. View

13.

Harms L, Burne T, Eyles D, McGrath J . Vitamin D and the brain. Best Pract Res Clin Endocrinol Metab. 2011; 25(4):657-69. DOI: 10.1016/j.beem.2011.05.009. View

14.

Faraco J, Morrison N, Baker A, Shine J, Frossard P . ApaI dimorphism at the human vitamin D receptor gene locus. Nucleic Acids Res. 1989; 17(5):2150. PMC: 317576. DOI: 10.1093/nar/17.5.2150. View

15.

Johnson D, Wagner C, Hulsey T, McNeil R, Ebeling M, Hollis B . Vitamin D deficiency and insufficiency is common during pregnancy. Am J Perinatol. 2010; 28(1):7-12. DOI: 10.1055/s-0030-1262505. View

16.

Morrison N, Qi J, Tokita A, Kelly P, Crofts L, Nguyen T . Prediction of bone density from vitamin D receptor alleles. Nature. 1994; 367(6460):284-7. DOI: 10.1038/367284a0. View

17.

Eyles D, Burne T, McGrath J . Vitamin D in fetal brain development. Semin Cell Dev Biol. 2011; 22(6):629-36. DOI: 10.1016/j.semcdb.2011.05.004. View

18.

Morrison N, Yeoman R, Kelly P, Eisman J . Contribution of trans-acting factor alleles to normal physiological variability: vitamin D receptor gene polymorphism and circulating osteocalcin. Proc Natl Acad Sci U S A. 1992; 89(15):6665-9. PMC: 49563. DOI: 10.1073/pnas.89.15.6665. View

19.

Koressaar T, Remm M . Enhancements and modifications of primer design program Primer3. Bioinformatics. 2007; 23(10):1289-91. DOI: 10.1093/bioinformatics/btm091. View

20.

Orton S, Morris A, Herrera B, Ramagopalan S, Lincoln M, Chao M . Evidence for genetic regulation of vitamin D status in twins with multiple sclerosis. Am J Clin Nutr. 2008; 88(2):441-7. PMC: 2740974. DOI: 10.1093/ajcn/88.2.441. View