Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

The Correlation Between Vitamin D Receptor (VDR) Gene Polymorphisms and Autism: A Meta-analysis


Vitamin D receptor (VDR) polymorphisms are risk factors for autism. We performed a systematic meta-analysis to explore the relationship between VDR gene polymorphisms and autism. A literature review of articles from Pubmed, Embase, the Cochrane Library, and Springer was conducted up to January 28, 2019. The association between SNPs and autism was calculated using pooled odd ratios (ORs) and 95% confidence intervals (CIs). Additionally, tests for heterogeneity, publication bias, and sensitivity were conducted. Six eligible studies with a total of 2001 participants (1045 cases and 956 controls) were included. Meta-analysis indicated that the “C” allele of the rs731236 gene, including C vs. T (OR = 1.3254, 95% CI = 1.0897–1.6122), CC vs. TT (OR = 2.0871, 95% CI = 1.3395–3.2519), and CC vs. TT + CT (OR = 1.9610, 95% CI = 1.2985–2.9615), might be a risk factor for autism. Moreover, the “G” allele of rs7975232 (G vs. T: OR = 0.8228, 95% CI = 0.6814–0.9934) was associated with a protective effect against the development of autism. No significant differences were found in the allele frequencies of rs11568820, rs1544410, and rs2228570 in the cases and controls. This meta-analysis revealed that both VDR rs731236 and rs7975232 were significantly associated with autism, whereas VDR rs11568820, rs1544410, and rs2228570 might not be correlated with the incidence of autism.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6


  1. Altun H, Kurutaş EB, Şahin N, Güngör O, Fındıklı E (2018) The levels of vitamin D, vitamin D receptor, homocysteine and complex B vitamin in children with autism spectrum disorders. Clinical Psychopharmacology and Neuroscience 16:383

  2. Balta B, Gumus H, Bayramov R et al (2018) Increased vitamin D receptor gene expression and rs11568820 and rs4516035 promoter polymorphisms in autistic disorder. Mol Biol Rep 45:1–6

  3. Cannell JJ, Grant WB (2013) What is the role of vitamin D in autism? Dermato-endocrinology 5:199–204

  4. Cieślińska A, Kostyra E, Chwała B et al (2017) Vitamin D receptor gene polymorphisms associated with childhood autism. Brain Sci 7:115

  5. Coşkun S, Şimşek Ş, Camkurt MA, Çim A, Çelik SB (2016) Association of polymorphisms in the vitamin D receptor gene and serum 25-hydroxyvitamin D levels in children with autism spectrum disorder. Gene 588:109–114

  6. Crane L, Chester JW, Goddard L, Henry LA, Hill E (2016) Experiences of autism diagnosis: a survey of over 1000 parents in the United Kingdom. Autism 20:153–162

  7. Kaneko I, Sabir MS, Dussik CM, Whitfield GK, Karrys A, Hsieh JC, Haussler MR, Meyer MB, Pike JW, Jurutka PW (2015) 1,25-Dihydroxyvitamin D regulates expression of the tryptophan hydroxylase 2 and leptin genes: implication for behavioral influences of vitamin D. FASEB J 29:4023–4035

  8. Lao JI (2014) Autism spectrum disorders: an intervention approach based on genomic analysis. Biology and Medicine 6:1

  9. Lau J, Ioannidis JP, Schmid CH (1997) Quantitative synthesis in systematic reviews. Ann Intern Med 127:820–826

  10. Lee YH, Kim J-H, Song GG (2014) Vitamin D receptor polymorphisms and susceptibility to Parkinson’s disease and Alzheimer’s disease: a meta-analysis. Neurol Sci 35:1947–1953

  11. Luchini C, Stubbs B, Solmi M, Veronese N (2017) Assessing the quality of studies in meta-analyses: advantages and limitations of the Newcastle Ottawa scale. World Journal of Meta-Analysis 5:80

  12. Máčová L, Bičíková M, Ostatníková D, Hill M, Stárka L (2017) Vitamin D, neurosteroids and autism. Physiol Res 66:S333–S340

  13. Minshew NJ, Goldstein G (2015) Autism as a disorder of complex information processing. Developmental Disabilities Research Reviews 4:129–136

  14. Omez N, Mingo LF, Bobadilla J, Serradilla F, Manzano JAC (2010) Particle swarm optimization models applied to neural networks using the R language. Wseas Transactions on Systems 9:192–202

  15. Ornoy A, Weinstein-Fudim L, Ergaz Z (2015) Prenatal factors associated with autism spectrum disorder (ASD). Reprod Toxicol 56:155–169

  16. Ozonoff S, Strayer DL, Mcmahon WM, Filloux F (2010) Executive function abilities in autism and Tourette syndrome: an information processing approach. J Child Psychol Psychiatry 35:1015–1032

  17. Peters JL, Sutton AJ, Jones DR, Abrams KR, Lesley R (2006) Comparison of two methods to detect publication bias in meta-analysis. Jama 295:676

  18. Reichow B, Wolery M (2009) Comprehensive synthesis of early intensive behavioral interventions for young children with autism based on the UCLA young autism project model. Journal of Autism & Developmental Disorders 39:23–41

  19. Ren-Nan F, Chen Z, Chang-Hao S, Ying L (2011) Meta-analysis of TNF 308 G/a polymorphism and type 2 diabetes mellitus. PLoS One 6:e18480

  20. Rodriguez S, Gaunt TR, Day IN (2009) Hardy-Weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies. Am J Epidemiol 169:505–514

  21. Saad K, Abdel-rahman AA, Elserogy YM, et al (2016). Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children. Nutritional neuroscience,19, 346-351

  22. Schmidt RJ, Hansen RL, Hartiala J, Allayee H, Sconberg JL, Schmidt LC, Volk HE, Tassone F (2015) Selected vitamin D metabolic gene variants and risk for autism spectrum disorders in the CHARGE study. Early Hum Dev 91:483–489

  23. Bozdogan ST, Kutuk MO, Tufan E, Altintas Z, Temel GO, Toros F (2018) No association between polymorphisms of vitamin D and oxytocin receptor genes and autistic spectrum disorder in a sample of Turkish children. Clinical Psychopharmacology and Neuroscience 16:415–421

  24. Smolders J, Damoiseaux J, Menheere P, Tervaert JWC, Hupperts R (2009) Fok-I vitamin D receptor gene polymorphism (rs10735810) and vitamin D metabolism in multiple sclerosis. J Neuroimmunol 207:117–121

  25. Taymans SE, Pack S, Pak E et al (2010) The human vitamin D receptor gene (VDR) is localized to region 12cen-q12 by fluorescent in situ hybridization and radiation hybrid mapping: genetic and physical VDR map. Journal of Bone & Mineral Research 14:1163–1166

  26. Volkmar FR (2011) Understanding the social brain in autism. Dev Psychobiol 53:428–434

  27. Zhang Z, Li S, Yu L, Liu J (2018) Polymorphisms in vitamin D receptor genes in association with childhood autism Spectrum disorder. Dis Markers 2018:1–7

Download references


This work was supported by the Shanghai Key Lab of Human Performance (Shanghai University of Sport) (Grant No. 11DZ2261100); Social Science Fund of Jiangsu Province (Grant No. 19TYD001); Fundamental Research Funds for the Central Universities (Grant No. 2018B59514); and Hohai University Disciplinary Planning Program (Grant No. 1013–418246).

Author information

HY conceived and designed the research, acquired data, analyzed data, drafted the manuscript, and conducted the statistical analysis. XW conceived and designed the research, analyzed data, obtained funding, and revised manuscript for important intellectual content. All authors read and approved the final manuscript.

Correspondence to Xueping Wu.

Ethics declarations

Ethics Approval and Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Availability of Data and Materials

Not applicable.

Competing Interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Yang, H., Wu, X. The Correlation Between Vitamin D Receptor (VDR) Gene Polymorphisms and Autism: A Meta-analysis. J Mol Neurosci 70, 260–268 (2020). https://doi.org/10.1007/s12031-019-01464-z

Download citation


  • Meta-analysis
  • Autism
  • Vitamin D receptor
  • Gene polymorphism