Association Of OGG1?DLST Promoter Methylation With Alzheimer's Disease In The Xinjiang Populations

Objective:Recent studies have identified multiple genes associated with Alzheimer's disease(AD)that is a neurodegenerative disorder,leading to progressive memory and cognitive impairment.The current study aimed to replicate the genetic associations of 5genes(OGG1,BIN1,SORL1,PSEN2,and NGF)with AD in Xinjiang Chinese population.In addition,we also evaluated the contribution of the promoter methylation of two genes(OGG1 and DLST)to the risk of AD.Methods:A total of 60-year-old hospitalized patients admitted to the First Affiliated Hospital of Xinjiang Medical University from April 2014 to 2015 were selected.By the experienced elderly medical department,neurologist in accordance with the American Psychiatric Association of Mental Disorders Diagnostic and Statistical Manual of the revised version of the Alzheimer's disease diagnostic criteria for diagnosis,in strict accordance with the standard screening cases.A total of 51 people were selected,the average age of the Han nationality(76.94 ± 6.93).There were 17 cases,7 males and 10 females with an average age of 75.65 ± 5.86 years.Meanwhile,the non-meta-data were matched with the baseline data of AD group living in the same area,age,educational status,blood pressure and disease status AD patients with34 as the control group,including 17 males and 17 females,the average age(77.59 ± 7.41)years old.Genotyping was performed using Sanger sequencing.The methylation level was measured using methylation-specific PCR.Results:(1)Compared with the control group,the frequency of APOE?4 allele was significantly higher than that of APOE?4 allele(?2 =9.36,P = 0.002).(2)There was no significant difference in genotype and allele of BIN1,SORL1,PSEN2,NGF,OGG1 between AD group and control group(P> 0.05).Based on whether the APOE?4 allele was further grouped and individuals carrying the APOE?4allele were genotype and allele frequencies in individuals with PSEN2,NGF,OGG1,SORL1 and BIN1 genes that did not carry APOE?4,There was no significant differencebetween the control groups(P> 0.05).(3)The methylation level of OGG1 gene in AD group was(0.012 ± 0.005),and the methylation level of OGG1 gene in control group was(0.012 ± 0.006),but there was no significant difference(t = 0.017,P = 0.987).There was no difference in methylation level of OGG1 gene between male and female in AD group and control group(P> 0.05).(4)According to whether the APOE?4 allele was carried out,it was found that in the AD group,the OGG1 methylation level of the individuals carrying the APOE?4 allele was(0.009 ± 0.003),and the individuals carrying the APOE?4 allele were(0.015 ± 0.006),the difference was statistically significant(t =-2.448,P = 0.027).After further stratification by sex,it was found that there was no difference in the methylation level of OGG1 gene between AD group and control group(P> 0.05)in both male and female,regardless of whether or not the APOE?4 allele was carried.In the AD group(0.023 ± 0.006)was significantly lower than that in the control group(0.033 ±0.028),the difference was statistically significant(Z =-2.212,P = 0.027).The DLST methylation level of female AD was significantly lower than that of the control group,and the difference was statistically significant(Z =-2.236,P = 0.025).(6)According to whether the APOE?4 allele was carried out,it was found that there was no statistically significant difference between the DLST methylation level and the individuals carrying the APOE?4 allele in the AD group and the control group,the individuals carrying the APOE?4 allele(P> 0.05).After further stratification by sex,it was found that DLST methylation level in female AD group was lower than that in control group,the difference was statistically significant(Z =-2.179,P = 0.029).Conclusion:(1)None of the SNP loci of OGG1(rs1052133),BIN1(rs744373),SORL1(rs1133174),PSEN2(rs8383),NGF(rs6330)were associated with the pathogenesis of AD.And the interaction between ApoE?4 and the above SNP locus of 5 genes was not associated with the pathogenesis of AD.(2)This study suggests that the low methylation status of the DLST gene may increase the risk of AD in the elderly population,especially in women.(3)This study suggests that the interaction of APOE?4 with OGG1 gene methylation may be related to the pathogenesis of AD.