Association of OGG1 and DLST promoter methylation with Alzheimer's disease in Xinjiang population.

ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disorder leading to progressive memory and cognitive impairment. Previous studies have identified multiple genes associated with AD. The aim of the present study was to validate the association of the five AD-associated variants, 8-oxoguanine DNA glycosylase 1 (OGG1) rs1052133, bridging integrator 1 rs744373, sortilin-related receptor 1, rs1133174, presenilin 2 rs8383, and nerve growth factor rs6330, in the Xinjiang Chinese population. In addition, the present study evaluated the contribution of the promoter methylation of two genes, OGG1 and dihydrolipoamide succinyltransferase (DLST) to the risk of AD. A total of 17 AD cases and 34 controls were recruited from Xinjiang province in China. Genotyping was done by Sanger sequencing. DNA methylation assay was performed using quantitative methylation specific polymerase chain reaction. The study was unable to repeat the previous association of the five genetic polymorphisms with AD. However, DLST methylation levels were demonstrated to be significantly decreased in AD patients (P=0.027), particularly in female AD patients (P=0.025). Subgroup analysis by apolipoprotein E (APOE ?4) genotype demonstrated that OGG1 methylation levels were significantly increased in APOE non-?4 carriers compared with APOE ?4 carriers (P=0.027). In summary, the present study reported that DLST hypomethylation was significantly associated with AD in females, and that OGG1 promoter methylation may interact with APOE ?4 genotype.

SUBMITTER: Chen W 

PROVIDER: S-EPMC6125839 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature