Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, P. R. China.
Hebei International Joint Research Center for Brain Science, Shijiazhuang, P. R. China.
J Alzheimers Dis. 2022;88(1):357-373. doi: 10.3233/JAD-220101.
The interactions between environmental factors and genetic variants have been implicated in the pathogenesis of Alzheimer's disease (AD). The altered gut microbiota (GM) and vitamin D deficiency are closely associated with the higher risk of AD.
This study was performed to evaluate whether the crosstalk between GM and single nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR) or vitamin D binding protein (VDBP) have a link with the risk of amnestic mild cognitive impairment (aMCI) in the Chinese elderly population.
A total of 171 aMCI patients and 261 cognitive normal controls (NC) were enrolled in this study. Six tag SNPs of VDR and VDBP were genotyped by PCR-RFLP. The serum levels of vitamin D, Aβ1-42, and p-tau (181P) were determined by using of ELISA kits. The alterations in the GM were analyzed by full-length 16S ribosomal RNA (rRNA) gene sequencing.
The frequencies of AG genotype and A allele of VDR rs1544410 in aMCI group were significantly higher than that in NC group (genotype: p = 0.002, allele: p = 0.003). Patients with aMCI showed an abnormal GM composition compared with NC group. Interestingly, significant differences in GM composition were found between aMCI and NC group among individuals with AG genotype, as well as between individuals with AG and GG genotype of VDR rs1544410 among patients with aMCI.
These results implicated that the crosstalk between gut microflora and vitamin D receptor variants are associated with the risk of aMCI in Chinese elderly population.
环境因素与遗传变异的相互作用与阿尔茨海默病（AD）的发病机制有关。肠道微生物群（GM）的改变和维生素 D 缺乏与 AD 风险的增加密切相关。
本研究旨在评估 GM 与维生素 D 受体（VDR）或维生素 D 结合蛋白（VDBP）单核苷酸多态性（SNP）之间的相互作用是否与中国老年人群发生遗忘型轻度认知障碍（aMCI）的风险有关。
本研究共纳入 171 例 aMCI 患者和 261 例认知正常对照者（NC）。采用 PCR-RFLP 法对 VDR 和 VDBP 的 6 个标签 SNP 进行基因分型。采用 ELISA 试剂盒检测血清维生素 D、Aβ1-42 和 p-tau（181P）水平。采用全长 16S rRNA 基因测序分析 GM 的变化。
与 NC 组相比，aMCI 组 VDR rs1544410 的 AG 基因型和 A 等位基因的频率显著升高（基因型：p=0.002，等位基因：p=0.003）。与 NC 组相比，aMCI 患者 GM 组成存在异常。有趣的是，在 VDR rs1544410 的 AG 基因型患者以及 aMCI 患者的 AG 和 GG 基因型患者之间，aMCI 和 NC 组之间的 GM 组成存在显著差异。
这些结果表明，肠道微生物群与维生素 D 受体变异之间的相互作用与中国老年人群发生 aMCI 的风险有关。
