阿尔茨海默病部分相关基因多态性及BAX、ApoE基因甲基化水平初探  

Preliminary study on the polymorphisms of some related genes and the methylation levels of BAX and ApoE genes in Alzheimer′s disease

作　　者：陈巍 周晓辉[1] 段亚丽 邹婷[1] 段世伟[3] 王钦文[3] 刘桂利 应秀茹 Chen Wei;Zhou Xiaohui;Duan Yali;Zou Ting;Duan Shiwei;Wang Qinwen;Liu Guili;Ying Xiuru(Department of Geriatrics,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China;Changji Branch of the First Affiliated Hospital of Xinjiang Medical University,Changji,Xinjiang 831100,China;Ningbo Key Lab of Behavior Neuroscience,Zhejiang Provincial Key Laboratory of Pathophysiology,School of Medicine,Ningbo University,Ningbo,Zhejiang 315211,China)

机构地区：[1]新疆医科大学第一附属医院老年病科,乌鲁木齐830054 [2]新疆医科大学第一附属医院昌吉分院,831100 [3]宁波市行为神经科学重点实验室,浙江省病理生理学重点实验室,宁波大学医学院,315211

出　　处：《中华神经科杂志》2021年第11期1119-1127,共9页Chinese Journal of Neurology

基　　金：新疆维吾尔自治区高技术研究发展项目(201517104)。

摘　　要：目的初步探讨5个候选基因(APH1B、PRNP、HMGCR、SIRT1、ApoE)的单核苷酸多态性(SNP)与阿尔茨海默病(AD)的关联性,同时分析BAX和ApoE基因启动子区甲基化水平对AD发病的影响。方法选取2014-2015年新疆医科大学第一附属医院老年病科收治的由老年医学科、神经内科医生根据美国精神病学会的精神障碍诊断和统计手册第4修订版中AD诊断标准诊断为很可能AD患者17例作为AD组,年龄(75.65±5.86)岁;选取同期住院的患者中年龄、性别、族别、受教育情况等基线资料与AD组相匹配的非AD患者34例作为对照组,年龄(77.59±7.41)岁。使用Sanger测序方法对候选基因进行SNP分型。使用甲基化特异性聚合酶链反应对DNA甲基化水平进行测定。结果ApoEε4等位基因在AD组与对照组间分布差异有统计学意义(χ^(2)=9.718,P=0.002)。候选基因(SIRT1 rs7895833、APH1B rs1047552、PRNP rs1799990、HMGCR rs3846662)SNP位点基因型及等位基因在AD组与对照组之间分布差异无统计学意义(P>0.05);按是否携带ApoEε4分层后在两组间也未发现差异有统计学意义(P>0.05)。AD组BAX启动子区甲基化水平(0.045±0.025)低于对照组(0.061±0.028)(t=-2.078,P=0.045),性别分层后,女性AD组BAX甲基化水平(0.044±0.021)低于对照组(0.065±0.275)(t=-2.230,P=0.045)。未发现ApoE启动子甲基化水平在AD组和对照组间差异有统计学意义(P>0.05),按是否携带ApoEε4分层后显示携带ApoEε4等位基因的AD患者甲基化水平(1.553±0.291)高于未携带者(1.221±0.261)(t=2.480,P=0.025)。结论ApoEε4等位基因可能是AD发病的危险因素。BAX启动子区的低甲基化状态可能与新疆老年人尤其是女性AD的发病相关。ApoEε4等位基因可能通过与ApoE甲基化间的相互作用导致AD的发病。Objective To preliminarily explore the association between single nucleotide polymorphisms(SNP)of five candidate genes(APH1B,PRNP,HMGCR,SIRT1,ApoE)and Alzheimer′s disease(AD),and to analyze the methylation levels of BAX and ApoE promoters on the pathogenesis of AD.Methods Seventeen cases who were admitted to the Department of Geriatrics of the First Affiliated Hospital of Xinjiang Medical University from 2014 to 2015 and diagnosed as likely to be AD by geriatrician and neurologists according to the AD diagnostic criteria in 4th Revised Edition of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association served AD group,with an age of(75.65±5.86)years,and 34 non-AD patients with matching baseline data such as age,gender,ethnicity,and education status among patients hospitalized during the same period were selected as control group,with an age of(77.59±7.41)years.Sanger sequencing method was used for SNP typing of candidate genes.Methylation-specific polymerase chain reaction was used to determine the DNA methylation level.Results The distribution of ApoEε4 allele was statistically different between the AD group and the control group(χ^(2)=9.718,P=0.002).Candidate genes(SIRT1 rs7895833,APH1B rs1047552,PRNP rs1799990,HMGCR rs3846662)SNP locus genotypes and alleles had no statistically significant differences in the distribution between the AD group and the control group(P>0.05).After stratification according to whether they carried ApoEε4,no statistically significant difference was found between the two groups(P>0.05).The BAX promoter methylation level of the AD group(0.045±0.025)was lower than that of the control group(0.061±0.028)(t=-2.078,P=0.045).After gender stratification,the BAX methylation level of the female AD group(0.044±0.021)was lower than that of the control group(0.065±0.275)(t=-2.230,P=0.045).There was no statistically significant difference in the methylation level of ApoE promoter between the AD group and the control group(P>0.05).After stratificat

关 键 词：阿尔茨海默病 多态性 单核苷酸 DNA甲基化 BAX基因 APOE基因 表观遗传学 

分 类 号：R749.16[医药卫生—神经病学与精神病学]