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

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),...

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Autores principales: Zou, Ting, Chen, Wei, Zhou, Xiaohui, Duan, Yali, Ying, Xiuru, Liu, Guili, Zhu, Meisheng, Pari, Abuliz, Alimu, Kader, Miao, Haijun, Kabinur, Keyim, Zhang, Lei, Wang, Qinwen, Duan, Shiwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons Australia, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899574/
https://www.ncbi.nlm.nih.gov/pubmed/30983028
http://dx.doi.org/10.1111/psyg.12440
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author Zou, Ting
Chen, Wei
Zhou, Xiaohui
Duan, Yali
Ying, Xiuru
Liu, Guili
Zhu, Meisheng
Pari, Abuliz
Alimu, Kader
Miao, Haijun
Kabinur, Keyim
Zhang, Lei
Wang, Qinwen
Duan, Shiwei
author_facet Zou, Ting
Chen, Wei
Zhou, Xiaohui
Duan, Yali
Ying, Xiuru
Liu, Guili
Zhu, Meisheng
Pari, Abuliz
Alimu, Kader
Miao, Haijun
Kabinur, Keyim
Zhang, Lei
Wang, Qinwen
Duan, Shiwei
author_sort Zou, Ting
collection PubMed
description 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) ε4 (P = 0.042). In the carriers of non‐APOE ε4, 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 ε4 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 ε4 and thus affected the pathogenesis of MCI. In addition, OGG1 promoter methylation interacted with several other factors to increase the risk of MCI.
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spelling pubmed-68995742019-12-19 Association of multiple candidate genes with mild cognitive impairment in an elderly Chinese Uygur population in Xinjiang Zou, Ting Chen, Wei Zhou, Xiaohui Duan, Yali Ying, Xiuru Liu, Guili Zhu, Meisheng Pari, Abuliz Alimu, Kader Miao, Haijun Kabinur, Keyim Zhang, Lei Wang, Qinwen Duan, Shiwei Psychogeriatrics Original Articles 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) ε4 (P = 0.042). In the carriers of non‐APOE ε4, 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 ε4 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 ε4 and thus affected the pathogenesis of MCI. In addition, OGG1 promoter methylation interacted with several other factors to increase the risk of MCI. John Wiley & Sons Australia, Ltd 2019-04-14 2019-11 /pmc/articles/PMC6899574/ /pubmed/30983028 http://dx.doi.org/10.1111/psyg.12440 Text en © 2019 The Authors. Psychogeriatrics published by John Wiley & Sons Australia, Ltd on behalf of Japanese Psychogeriatric Society This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Zou, Ting
Chen, Wei
Zhou, Xiaohui
Duan, Yali
Ying, Xiuru
Liu, Guili
Zhu, Meisheng
Pari, Abuliz
Alimu, Kader
Miao, Haijun
Kabinur, Keyim
Zhang, Lei
Wang, Qinwen
Duan, Shiwei
Association of multiple candidate genes with mild cognitive impairment in an elderly Chinese Uygur population in Xinjiang
title Association of multiple candidate genes with mild cognitive impairment in an elderly Chinese Uygur population in Xinjiang
title_full Association of multiple candidate genes with mild cognitive impairment in an elderly Chinese Uygur population in Xinjiang
title_fullStr Association of multiple candidate genes with mild cognitive impairment in an elderly Chinese Uygur population in Xinjiang
title_full_unstemmed Association of multiple candidate genes with mild cognitive impairment in an elderly Chinese Uygur population in Xinjiang
title_short Association of multiple candidate genes with mild cognitive impairment in an elderly Chinese Uygur population in Xinjiang
title_sort association of multiple candidate genes with mild cognitive impairment in an elderly chinese uygur population in xinjiang
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899574/
https://www.ncbi.nlm.nih.gov/pubmed/30983028
http://dx.doi.org/10.1111/psyg.12440
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