Association of multiple candidate genes with mild cognitive impairment in an elderly Chinese Uygur population in Xinjiang
| Autor: | Qinwen Wang, Wei Chen, Haijun Miao, Lei Zhang, Shiwei Duan, Kader Alimu, Ting Zou, Guili Liu, Abuliz Pari, Xiaohui Zhou, Meisheng Zhu, Xiuru Ying, Yali Duan, Keyim Kabinur |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Apolipoprotein E
DLST Male Candidate gene medicine.medical_specialty SORL1 Population Apolipoprotein E4 interaction Dihydrolipoyllysine-Residue Acetyltransferase Autoantigens Polymerase Chain Reaction DNA Glycosylases Mitochondrial Proteins 03 medical and health sciences 0302 clinical medicine Asian People Internal medicine PSEN2 mental disorders Ethnicity Medicine Humans Cognitive Dysfunction education Promoter Regions Genetic Genotyping OGG1 Aged Aged 80 and over education.field_of_study Polymorphism Genetic 030214 geriatrics business.industry Methylation Original Articles MCI Psychiatry and Mental health Endocrinology APOE ε4 DNA methylation Original Article Female methylation Geriatrics and Gerontology business Gerontology 030217 neurology & neurosurgery Acyltransferases |
| Zdroj: | Psychogeriatrics |
| ISSN: | 1479-8301 1346-3500 |
| Popis: | 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) e4 (P = 0.042). In the carriers of non-APOE e4, 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 e4 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 e4 and thus affected the pathogenesis of MCI. In addition, OGG1 promoter methylation interacted with several other factors to increase the risk of MCI. |
| Databáze: | OpenAIRE |
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