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

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 (FokI, BsmI, TaqI, and ApaI) 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 ApaI polymorphism decreased the overall AD risk, and the TaqI increased the overall PD susceptibility. In addition, the BsmI and ApaI polymorphisms were significantly correlated with the overall MCI risk. Stratified analysis by ethnicity further showed that the TaqI and ApaI genotypes reduced the AD predisposition among Caucasians, while the TaqI polymorphism enhanced the PD risk among Asians. Intriguingly, carriers with the BB genotype significantly decreased the MCI risk in Asian descents, and the ApaI 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.

Keywords: Alzheimer’s disease; Parkinson’s disease; VDR; gene polymorphism; meta-analysis; mild cognitive impairment; susceptibility.

FIGURE 1

Flow diagram of the eligible study selection process.

FIGURE 2

Forest plots for the association between VDR ApaI polymorphism and AD risk in five models. (A) Allele model; (B) homozygote model; (C) heterozygote model; (D) dominant model; (E) recessive model.

FIGURE 3

Forest plots for the association between VDR TaqI polymorphism and PD risk in five models. (A) Allele model; (B) homozygote model; (C) heterozygote model; (D) dominant model; (E) recessive model.

FIGURE 4

Forest plots for the association between VDR BsmI polymorphism and MCI risk in five models. (A) Allele model; (B) homozygote model; (C) heterozygote model; (D) dominant model; (E) recessive model.

FIGURE 5

Forest plots for the association between VDR ApaI polymorphism and MCI risk in five models. (A) Allele model; (B) homozygote model; (C) heterozygote model; (D) dominant model; (E): recessive model.

FIGURE 6

Sensitivity analysis for VDR gene polymorphism and PD risk in dominant model. (A) FokI polymorphism; (B): BsmI polymorphism; (C) TaqI polymorphism; (D) ApaI polymorphism.

FIGURE 7

Egger’s linear regression plot for detecting the publication bias in the dominant model of VDR SNPs. (A) FokI polymorphism and AD risk; (B) BsmI polymorphism and AD risk; (C) TaqI polymorphism and AD risk; (D) ApaI polymorphism and AD risk; (E) FokI polymorphism and PD risk; (F) BsmI polymorphism and PD risk; (G) TaqI polymorphism and PD risk; (H) ApaI polymorphism and PD risk; (I) FokI polymorphism and MCI risk; (J) BsmI polymorphism and MCI risk; (K) TaqI polymorphism and MCI risk; (L) ApaI polymorphism and MCI risk.