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Association of multiple candidate genes with mild cognitive impairment in an elderly Chinese Uygur population in Xinjiang
Author(s) -
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
Publication year - 2019
Publication title -
psychogeriatrics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 32
eISSN - 1479-8301
pISSN - 1346-3500
DOI - 10.1111/psyg.12440
Subject(s) - cognitive impairment , association (psychology) , cognition , candidate gene , chinese population , medicine , gene , population , genetics , traditional medicine , psychology , psychiatry , biology , environmental health , genotype , psychotherapist
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.