Crosstalk Between Gut Microflora and Vitamin D Receptor SNPs Are Associated with the Risk of Amnestic Mild Cognitive Impairment in a Chinese Elderly Population

Article type: Research Article

Authors: Zhang, Kaixia^{a; 1} | Ma, Xiaoying^{a; 1} | Zhang, Rui^{a; b; c} | Liu, Zanchao^d | Jiang, Lei^{a; b; c} | Qin, Yushi^a | Zhang, Di^a | Tian, Pei^a | Gao, ZhaoYu^{a; b; c} | Zhang, Nan^{a; b; c} | Shi, Zhongli^{a; b; c} | Xu, Shunjiang^{a; b; c; e; *}

Affiliations: [a] Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, P. R. China | [b] Hebei International Joint Research Center for Brain Science, Shijiazhuang, P. R. China | [c] Hebei Key Laboratory of Brain Science and Psychiatric-Psychologic Disease, Shijiazhuang, P. R. China | [d] Department of Endocrinology, The Second Hospital of Shijiazhuang City, Shijiazhuang, P. R. China | [e] Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, ChineseAcademy of Medical Sciences, Beijing, P. R. China

Correspondence: [*] Correspondence to: Shunjiang Xu, Central Laboratory, The First Hospital of Hebei Medical University, No. 89, Donggang Road, Shijiazhuang, 050031, P. R. China. Tel.: +86 311 8591 7257; Fax: +86 311 8591 7290; E-mail: sjxu66@hotmail.com; ORCID: https://orcid.org/0000-0002-9441-3900.

Note: [1] These authors contributed equally to this work.

Abstract: Background: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. Objective: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. Methods: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. Results: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. Conclusion: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.

Keywords: Amnestic mild cognitive impairment, full-length 16S rRNA sequencing, gut microbiota, single nucleotide polymorphisms, vitamin D receptor

DOI: 10.3233/JAD-220101

Journal: Journal of Alzheimer's Disease, vol. 88, no. 1, pp. 357-373, 2022