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 VDRgene 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 ApaIrs7975232, BsmIrs1544410, FokIrs10735810, and TaqIrs731236 were included in the meta-analysis. The global assessment indicated an association between the BsmIpolymorphism 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 ApaIpolymorphism 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 TaqIpolymorphism of the VDRgene and increased odds of AD, particularly for Caucasian subjects. Egger's linear regression test found no publication bias. This meta-analysis indicated that VDR ApaIand BsmI, and TaqIgene 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.Statement of Significance: Compared with previous studies on the same subject, this study included more data and found that the dominant and homozygous gene models of a TaqIgene polymorphism may increase the risk of Alzheimer disease. This study investigated the association between vitamin D receptor gene polymorphisms and mild cognitive impairment and for the first time indicated that the allele, dominant, and heterozygous gene models of BsmIpolymorphisms are related to an increased risk of mild cognitive impairment.