A systematic review and meta-analysis of the associations of vitamin D receptor genetic variants with two types of most common neurodegenerative disorders

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Whether vitamin D receptor (VDR) genetic variants influence individual susceptibility to neurodegenerative disorders remains controversial.


This meta-analysis was conducted to analyze correlations of VDR genetic variants with two types of most common neurodegenerative disorders, Parkinson’s disease (PD) and Alzheimer’s disease (AD).


Systematic literature research of PubMed and Embase was performed to identify eligible articles. Q test and I2 statistic were employed to decide whether pooled analyses would be performed with random-effect models (REMs) or fixed-effect models (FEMs). All statistical analyses were conducted with Review Manager.


Totally sixteen studies were enrolled for analyses. Among these eligible studies, ten studies were about PD (2356 cases and 2815 controls) and six studies were about AD (1256 cases and 1205 controls). Pooled overall analyses suggested that VDR rs7975232 (additive model: p = 0.03, OR = 1.19, 95% CI 1.01–1.39) and rs2228570 (recessive model: p < 0.008, OR = 1.26, 95% CI 1.06–1.50; allele model: p < 0.001, OR = 0.80, 95% CI 0.71–0.91) variants were significantly correlated with PD, and VDR rs731236 (dominant model: p = 0.003, OR = 0.70, 95% CI 0.56–0.89; additive model: p = 0.02, OR = 1.32, 95% CI 1.06–1.66; allele model: p = 0.02, OR = 0.82, 95% CI 0.69–0.96) variant was significantly correlated with AD. Further subgroup analyses by ethnicity revealed that the positive results were mainly driven by the Asians, whereas no significant associations were observed in Caucasians.


Our meta-analysis suggested that VDR rs7975232 and rs2228570 variants might serve as genetic biomarkers of PD, whereas VDR rs731236 variant might serve as a genetic biomarker of AD.

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Fig. 1


  1. 1.

    Winner B, Kohl Z, Gage FH (2011) Neurodegenerative disease and adult neurogenesis. Eur J Neurosci 33:1139–1151

  2. 2.

    Bertram L, Tanzi RE (2005) The genetic epidemiology of neurodegenerative disease. J Clin Invest 115:1449–1457

  3. 3.

    Ramanan VK, Saykin AJ (2013) Pathways to neurodegeneration: mechanistic insights from GWAS in Alzheimer’s disease, Parkinson’s disease, and related disorders. Am J Neurodegener Dis 2:145–175

  4. 4.

    Purro SA, Galli S, Salinas PC (2014) Dysfunction of Wnt signaling and synaptic disassembly in neurodegenerative diseases. J Mol Cell Biol 6:75–80

  5. 5.

    Kiraly SJ, Kiraly MA, Hawe RD et al (2006) Vitamin D as a neuroactive substance: review. ScientificWorldJournal 6:125–139

  6. 6.

    van den Bos F, Speelman AD, van Nimwegen M et al (2013) Bone mineral density and vitamin D status in Parkinson’s disease patients. J Neurol 260:754–760

  7. 7.

    Wilkins CH, Birge SJ, Sheline YI et al (2009) Vitamin D deficiency is associated with worse cognitive performance and lower bone density in older African Americans. J Natl Med Assoc 101:349–354

  8. 8.

    Jang W, Kim HJ, Li H et al (2014) 1,25-Dyhydroxyvitamin D3 attenuates rotenone-induced neurotoxicity in SH-SY5Y cells through induction of autophagy. Biochem Biophys Res Commun 451:142–147

  9. 9.

    Jang W, Park HH, Lee KY et al (2015) 1,25-dyhydroxyvitamin D3 attenuates L-DOPA-induced neurotoxicity in neural stem cells. Mol Neurobiol 51:558–570

  10. 10.

    Li H, Jang W, Kim HJ et al (2015) Biochemical protective effect of 1,25-dihydroxyvitamin D3 through autophagy induction in the MPTP mouse model of Parkinson’s disease. Neuroreport 26:669–674

  11. 11.

    Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151:264–269

  12. 12.

    Stang A (2010) Critical evaluation of the Newcastle–Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603–605

  13. 13.

    Setodji CM, Shwartz M (2013) Fixed-effect or random-effect models: what are the key inference issues? Med Care 51:25–27

  14. 14.

    Uitterlinden AG, Fang Y, Van Meurs JB et al (2014) Genetics and biology of vitamin D receptor polymorphisms. Gene 338:143–156

  15. 15.

    Valdivielso JM, Fernandez E (2006) Vitamin D receptor polymorphisms and diseases. Clin Chim Acta 371:1–12

  16. 16.

    Xie X, Shi X, Liu M (2017) The roles of TLR gene variants in atherosclerosis: a systematic review and meta-analysis of 35,317 subjects. Scand J Immunol 86:50–58

  17. 17.

    Shi X, Xie X, Jia Y et al (2016) Associations of insulin receptor and insulin receptor substrates genetic variants with polycystic ovary syndrome: a systematic review and meta-analysis. J Obstet Gynaecol Res 42:844–854

  18. 18.

    Xie X, Shi X, Xun X et al (2017) Endothelial nitric oxide synthase gene single nucleotide variants and the susceptibility of hypertension: a meta-analysis involving 63,258 subjects. Clin Exp Hypertens 39:175–182

  19. 19.

    Zhu Y, Zheng G, Hu Z (2018) Association between SERT insertion/deletion polymorphism and the susceptibility of irritable bowel syndrome: a meta-analysis based on 7039 subjects. Gene 679:133–137

  20. 20.

    Sun H, Li Q, Jin Y et al (2018) Associations of tumor necrosis factor-α variants with the susceptibility of asthma: a meta-analysis. Exp Mol Pathol.

  21. 21.

    Hu Z, He C (2017) CDKN2B gene rs1063192 polymorphism decreases the risk of glaucoma. Oncotarget 8:21167–21176

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Author information

JG, JL and YH conceived of the study, participated in its design. JG and JZ conducted the systematic literature review. FY and XL performed data analyses. JG, JL and YH drafted the manuscript. All gave final approval and agree to be accountable for all aspects of work ensuring integrity and accuracy.

Correspondence to Jijun Liu or Yuanchi Huang.

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Geng, J., Zhang, J., Yao, F. et al. A systematic review and meta-analysis of the associations of vitamin D receptor genetic variants with two types of most common neurodegenerative disorders. Aging Clin Exp Res 32, 21–27 (2020) doi:10.1007/s40520-019-01135-4

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  • Vitamin D receptor (VDR)
  • Gene variants
  • Neurodegenerative disorders
  • Parkinson’s disease (PD)
  • Alzheimer’s disease (AD)
  • Meta-analysis