Vitamin D Receptor Gene Polymorphisms and Risk of Alzheimer Disease and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis

The results from epidemiologic studies suggest that vitamin D receptor (VDR) gene polymorphisms are potentially associated with Alzheimer disease (AD) and mild cognitive impairment (MCI), but this association has yet to be confirmed. Here, we conducted a meta-analysis based on a larger sample size to clarify the contribution of VDR gene polymorphisms to MCI and AD susceptibility. The PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure databases were searched to obtain studies published before 30 October, 2020. The case group includes MCI and AD patients, and the matched controls were without any cognitive complaints. ORs and 95% CIs were used to assess the strength of the association. Ten case-control studies with 3573 participants and 4 loci of ApaI rs7975232, BsmI rs1544410, FokI rs10735810, and TaqI rs731236 were included in the meta-analysis. The global assessment indicated an association between the BsmI polymorphism and increased odds of MCI in the allelic model (b compared with B; OR: 1.77; 95% CI: 1.24, 2.54), the dominant model (bb + Bb compared with BB; OR: 2.04; 95% CI: 1.32, 3.16), and the heterozygote model (Bb compared with BB; OR: 1.97; 95% CI: 1.26, 3.09). In contrast, the ApaI polymorphism was protective against MCI in all models. The dominant model (tt + Tt compared with TT; OR: 1.44; 95% CI: 1.17, 1.79) and the homozygous model (tt compared with TT; OR: 1.43; 95% CI: 1.02, 2.00) revealed an association between the TaqI polymorphism of the VDR gene and increased odds of AD, particularly for Caucasian subjects. Egger's linear regression test found no publication bias. This meta-analysis indicated that VDR ApaI and BsmI, and TaqI gene polymorphisms may be important predictors of MCI and AD, respectively, with population discrepancies. More research is needed to further confirm these associations, especially considering gene-gene interactions, gene-environment interactions, and other confounding factors.