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Association of multiple candidate genes with mild cognitive impairment in an elderly Chinese Uygur population in Xinjiang.

ABSTRACT: BACKGROUND:Mild cognitive impairment (MCI) is a high-risk factor for Alzheimer's disease (AD). In the present study, we investigated the association of genetic polymorphisms of five genes (8-oxoguanine DNA glycosylase 1 (OGG1), bridging integrator 1 (BIN1), sortilin-related receptor 1 (SORL1), presenilin 2 (PSEN2) and nerve growth factor (NGF)) with MCI risk in a Xinjiang Uygur population. We also tested the relationship between the promoter methylation of genes OGG1 and dihydrolipoamide S-succinyltransferase (DLST) with MCI. METHODS:This study involved 43 MCI patients and 125 controls. Genotyping was done by Sanger sequencing. DNA methylation assays used quantitative methylation-specific polymerase chain reaction. RESULTS:We found that polymorphisms of five genes and the methylation of DLST and OGG1 genes were not associated with MCI (P?>?0.05). Further subgroup analysis found that DLST hypomethylation was significantly associated with MCI in the carriers of apolipoprotein E (APOE) ?4 (P?=?0.042). In the carriers of non-APOE ?4, DLST methylation levels were significantly lower in the male control group than in the female control group (p?=?0.04). Meanwhile, among the non-APOE ?4 carriers younger than 75, OGG1 hypermethylation levels were significantly associated with MCI (P?=?0.049). DLST methylation in female controls was significantly lower than that in male controls (P?=?0.003). According to gender stratification, there was a significant positive correlation of fasting plasma glucose (FBG) and high-density lipoprotein (HDL) with OGG1 methylation in the female controls (FBG: P?=?0.024; HDL: P?=?0.033). There was a significant inverse correlation between low-density lipoprotein and DLST methylation in male MCI (P?=?0.033). There was a significant positive correlation between HDL and DLST methylation levels in the female controls (P?=?0.000). CONCLUSIONS:This study was the first to discover that DLST promoter methylation interacted with APOE ?4 and thus affected the pathogenesis of MCI. In addition, OGG1 promoter methylation interacted with several other factors to increase the risk of MCI.

SUBMITTER: Zou T

PROVIDER: S-EPMC6899574 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Association of multiple candidate genes with mild cognitive impairment in an elderly Chinese Uygur population in Xinjiang.

Zou Ting T Chen Wei W Zhou Xiaohui X Duan Yali Y Ying Xiuru X Liu Guili G Zhu Meisheng M Pari Abuliz A Alimu Kader K Miao Haijun H Kabinur Keyim K Zhang Lei L Wang Qinwen Q Duan Shiwei S

Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society 20190414 6

<h4>Background</h4>Mild cognitive impairment (MCI) is a high-risk factor for Alzheimer's disease (AD). In the present study, we investigated the association of genetic polymorphisms of five genes (8-oxoguanine DNA glycosylase 1 (OGG1), bridging integrator 1 (BIN1), sortilin-related receptor 1 (SORL1), presenilin 2 (PSEN2) and nerve growth factor (NGF)) with MCI risk in a Xinjiang Uygur population. We also tested the relationship between the promoter methylation of genes OGG1 and dihydrolipoamide ...[more]

PMID: 30983028

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Project description:BackgroundMild cognitive impairment (MCI) is a kind of non-functional cognitive decline between normal aging and dementia. With the increase of individual age, the quality of cognitive function has become a more and more important topic. The study of gene loci in patients with MCI is essential for the prevention of dementia. In this study, we evaluate the gene polymorphism in Chinese Han patients with MCI by propensity score matching (PSM) and comparing them to healthy control (HC) subjects.MethodsFour hundred seventeen patients with mild cognitive impairment and 508 healthy people were included. The two groups were matched by applying one-to-one PSM, and the matching tolerance was set to 0.002. The matching covariates included gender,age,occupation,marital status,living mode. Then, a case-control associated analysis was conducted to analyze the genotype and allele frequencies of single nucleotide polymorphisms (SNPs) in the MCI group and the control group.ResultsThree hundred eleven cases were successfully matched in each group, and there was no statistical difference on all the matching variables, gender, age, occupation, marital status, living mode between two groups after the match (P > 0.05). The allele frequency of bridging integrator 1(BIN1) rs7561528 showed minimal association with MCI in the Han Chinese population (P = 0.01). Compared with the healthy control (HC) group, A allele frequency of MCI group patients was significantly decreased. The genotype frequency of BIN1 rs6733839 showed minimal association with MCI in the recessive model (P = 0.03). The genotype frequency of rs7561528 showed minimal association with MCI in the codominant, dominant, overdominant, and log-additive model (P < 0.05). The genotype frequencies of StAR-related lipid transfer domain 6 (STARD6) rs10164112 showed nominal association with MCI in the codominant, dominant, and log-additive model (P < 0.05). Unfortunately, the significant differences did not survive Benjamini-Hochberg false discovery rate correction (adjusted P > 0.05). The patients with SPI1 rs1057233 may be the protective factor of MCI (OR = 0.733, 95%CI 0.625-0.859, P < 0.001), and patients with APOE rs10164112 may be a risk factor for MCI (OR = 1.323, 95%CI 1.023-1.711, P = 0.033).ConclusionsThe polymorphisms of rs7561528, rs6733839 loci in the BIN1 gene, and rs1057233 loci in the SPI1 gene may be associated with the MCI in Chinese Han population. APOE gene was the risk factor of MCI, but further verification in a large sample population is still needed.

Dataset Information

Association of multiple candidate genes with mild cognitive impairment in an elderly Chinese Uygur population in Xinjiang.

Publications

Association of multiple candidate genes with mild cognitive impairment in an elderly Chinese Uygur population in Xinjiang.

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