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

Abstract

Background

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

Aims

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).

Methods

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.

Results

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.

Conclusion

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.

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

Fig. 1

References

  1. 1.

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

    Article  Google Scholar 

  2. 2.

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

    CAS  Article  Google Scholar 

  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

    PubMed  PubMed Central  Google Scholar 

  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

    CAS  Article  Google Scholar 

  5. 5.

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

    CAS  Article  Google Scholar 

  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

    CAS  Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    CAS  Article  Google Scholar 

  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

    CAS  Article  Google Scholar 

  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

    CAS  Article  Google Scholar 

  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

    Article  Google Scholar 

  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

    Article  Google Scholar 

  13. 13.

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

    Article  Google Scholar 

  14. 14.

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

    Article  Google Scholar 

  15. 15.

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

    CAS  Article  Google Scholar 

  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

    CAS  Article  Google Scholar 

  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

    CAS  Article  Google Scholar 

  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

    CAS  Article  Google Scholar 

  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

    CAS  Article  Google Scholar 

  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. https://doi.org/10.1016/j.yexmp.2018.08.012

    Article  PubMed  Google Scholar 

  21. 21.

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

    PubMed  PubMed Central  Google Scholar 

Download references

Funding

None.

Author information

Affiliations

Authors

Contributions

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.

Corresponding authors

Correspondence to Jijun Liu or Yuanchi Huang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study formal consent is not required.

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

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). https://doi.org/10.1007/s40520-019-01135-4

Download citation

Keywords

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