Associations of Vitamin D Receptor Polymorphisms with Risk of Alzheimer's Disease, Parkinson's Disease, and Mild Cognitive Impairment: a Systematic Review and Meta-analysis

Overview

Journal Front Aging Neurosci

Specialty Geriatrics

Date 2024 Apr 29

PMID 38681668

Authors

Yanjun Du

Peizhen Geng

Qunqun Chen

Laixi Han

Lu Liu

Maoquan Yang

Mingzhu Tan

Jun Meng

Xiaojuan Sun

Lidan Feng

Affiliations

Soon will be listed here.

Abstract

Vitamin D is a lipid soluble steroid hormone, which plays a critical role in the calcium homeostasis, neuronal development, cellular differentiation, and growth by binding to vitamin D receptor (VDR). Associations between VDR gene polymorphism and Alzheimer's disease (AD), Parkinson's disease (PD), and mild cognitive impairment (MCI) risk has been investigated extensively, but the results remain ambiguous. The aim of this study was to comprehensively assess the correlations between four VDR polymorphisms (I, I, I, and I) and susceptibility to AD, PD, and MCI. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to determine the relationship of interest. Pooled analyses suggested that the I polymorphism decreased the overall AD risk, and the I increased the overall PD susceptibility. In addition, the I and I polymorphisms were significantly correlated with the overall MCI risk. Stratified analysis by ethnicity further showed that the I and I genotypes reduced the AD predisposition among Caucasians, while the I polymorphism enhanced the PD risk among Asians. Intriguingly, carriers with the BB genotype significantly decreased the MCI risk in Asian descents, and the I variant elevated the predisposition to MCI in Caucasians and Asians. Further studies are need to identify the role of VDR polymorphisms in AD, PD, and MCI susceptibility.

References

Tanaka K, Miyake Y, Fukushima W, Kiyohara C, Sasaki S, Tsuboi Y . Vitamin D receptor gene polymorphisms, smoking, and risk of sporadic Parkinson's disease in Japan. Neurosci Lett. 2017; 643:97-102. DOI: 10.1016/j.neulet.2017.02.037. View

Enjuanes A, Garcia-Giralt N, Supervia A, Nogues X, Mellibovsky L, Carbonell J . Regulation of CYP19 gene expression in primary human osteoblasts: effects of vitamin D and other treatments. Eur J Endocrinol. 2003; 148(5):519-26. DOI: 10.1530/eje.0.1480519. View

Agliardi C, Guerini F, Zanzottera M, Bolognesi E, Meloni M, Riboldazzi G . The VDR FokI (rs2228570) polymorphism is involved in Parkinson's disease. J Neurol Sci. 2021; 428:117606. DOI: 10.1016/j.jns.2021.117606. View

Scherzer C, Eklund A, Morse L, Liao Z, Locascio J, Fefer D . Molecular markers of early Parkinson's disease based on gene expression in blood. Proc Natl Acad Sci U S A. 2007; 104(3):955-60. PMC: 1766335. DOI: 10.1073/pnas.0610204104. View

Beecham G, Martin E, Li Y, Slifer M, Gilbert J, Haines J . Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease. Am J Hum Genet. 2009; 84(1):35-43. PMC: 2668056. DOI: 10.1016/j.ajhg.2008.12.008. View

Gezen-Ak D, Dursun E, Ertan T, Hanagasi H, Gurvit H, Emre M . Association between vitamin D receptor gene polymorphism and Alzheimer's disease. Tohoku J Exp Med. 2007; 212(3):275-82. DOI: 10.1620/tjem.212.275. View

Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L . Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol. 2006; 5(3):228-34. DOI: 10.1016/S1474-4422(06)70355-6. View

Schlogl M, Holick M . Vitamin D and neurocognitive function. Clin Interv Aging. 2014; 9:559-68. PMC: 3979692. DOI: 10.2147/CIA.S51785. View

de Lau L, Breteler M . Epidemiology of Parkinson's disease. Lancet Neurol. 2006; 5(6):525-35. DOI: 10.1016/S1474-4422(06)70471-9. View

10.

Nelson P, Alafuzoff I, Bigio E, Bouras C, Braak H, Cairns N . Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. J Neuropathol Exp Neurol. 2012; 71(5):362-81. PMC: 3560290. DOI: 10.1097/NEN.0b013e31825018f7. View

11.

Uitterlinden A, Fang Y, van Meurs J, Pols H, van Leeuwen J . Genetics and biology of vitamin D receptor polymorphisms. Gene. 2004; 338(2):143-56. DOI: 10.1016/j.gene.2004.05.014. View

12.

Gauthier S, Reisberg B, Zaudig M, Petersen R, Ritchie K, Broich K . Mild cognitive impairment. Lancet. 2006; 367(9518):1262-70. DOI: 10.1016/S0140-6736(06)68542-5. View

13.

Suzuki M, Yoshioka M, Hashimoto M, Murakami M, Kawasaki K, Noya M . 25-hydroxyvitamin D, vitamin D receptor gene polymorphisms, and severity of Parkinson's disease. Mov Disord. 2012; 27(2):264-71. DOI: 10.1002/mds.24016. View

14.

Yagyu K, Kitagawa K, Wu B, Zhang N, Irie T, Hattori N . Protective effects of estradiol against amyloid beta protein-induced inhibition of neuronal Cl(-)-ATPase activity. Neuropharmacology. 2003; 43(8):1297-304. DOI: 10.1016/s0028-3908(02)00304-0. View

15.

Wacholder S, Chanock S, Garcia-Closas M, El Ghormli L, Rothman N . Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. J Natl Cancer Inst. 2004; 96(6):434-42. PMC: 7713993. DOI: 10.1093/jnci/djh075. View

16.

Keeney J, Butterfield D . Vitamin D deficiency and Alzheimer disease: Common links. Neurobiol Dis. 2015; 84:84-98. DOI: 10.1016/j.nbd.2015.06.020. View

17.

Eyles D, Smith S, Kinobe R, Hewison M, McGrath J . Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat. 2004; 29(1):21-30. DOI: 10.1016/j.jchemneu.2004.08.006. View

18.

Moher D, Liberati A, Tetzlaff J, Altman D . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009; 6(7):e1000097. PMC: 2707599. DOI: 10.1371/journal.pmed.1000097. View

19.

Amtul Z, Wang L, Westaway D, Rozmahel R . Neuroprotective mechanism conferred by 17beta-estradiol on the biochemical basis of Alzheimer's disease. Neuroscience. 2010; 169(2):781-6. DOI: 10.1016/j.neuroscience.2010.05.031. View

20.

Hodson R . Alzheimer's disease. Nature. 2018; 559(7715):S1. DOI: 10.1038/d41586-018-05717-6. View