尿酸介导OPRD1基因低甲基化影响阿尔茨海默病  

Uric acid mediated hypomethylation of OPRD1 gene affects Alzheimer’s disease

作　　者：陈瑶 陈勇[1] 应颖[1] 范剑波 耿保庆 郑成应 徐婷 傅浩源 张韵格 陈吉 CHEN Yao;CHEN Yong;YING Ying;FAN Jianbo;GENG Baoqing;ZHENG Chengying;XU Ting;FU Haoyuan;ZHANG Yunge;CHEN Ji(Ningbo No.2 Hospital,Ningbo 315010,China;Taizhou Hospital of Zhejiang,Taizhou 317099,China;Zhenhai Longsai Hospital,Ningbo 315299,China;Ningbo Kangning Hospital,Ningbo 315201,China;The Third People’s Hospital Health Care Group of Cixi(Chang He Branch),Ningbo 315325,China;Health Science Center,Ningbo University,Ningbo 315211,China)

机构地区：[1]宁波市第二医院,浙江宁波315010 [2]浙江省台州医院,浙江台州317099 [3]宁波市镇海龙赛医院,浙江宁波315299 [4]宁波市康宁医院,浙江宁波315201 [5]慈溪市第三人民医院医疗健康集团长河分院,浙江宁波315325 [6]宁波大学医学部,浙江宁波315211

出　　处：《宁波大学学报（理工版）》2023年第4期78-88,共11页Journal of Ningbo University：Natural Science and Engineering Edition

基　　金：浙江省医学科学研究基金(2020KY328,2020KY268).

摘　　要：探讨OPRD1基因甲基化与尿酸及阿尔茨海默病的相关性,并在细胞实验中证实尿酸可影响OPRD1基因甲基化水平.采集阿尔茨海默病组、高尿酸血症组及健康对照组的静脉血,检测OPRD1基因甲基化水平,并探讨与尿酸水平的相关性.细胞实验中,采用不同尿酸浓度先后处理细胞,分别检测OPRD1基因甲基化水平.结果表明,高尿酸血症组OPRD1基因pos2、pos4位点甲基化水平低于健康对照组,阿尔茨海默病组pos4位点甲基化水平高于健康对照组,尿酸水平与OPRD1基因甲基化水平负相关,高浓度尿酸下细胞OPRD1基因pos2、pos3、pos4位点的甲基化水平更低.由此得出尿酸可能通过介导OPRD1基因pos4位点的低甲基化修饰,从而影响阿尔茨海默病的发病.The present study was aimed to investigate the correlation between OPRD1 gene methylation,uric acid and Alzheimer’s disease.It also examined whether uric acid could affect OPRD1 gene methylation in vitro.The venous blood of the patients with Alzheimer’s disease,the hyperuricemia group and the healthy control group was collected.The cells were successively treated with different concentrations of uric acid and the methylation level of OPRD1 gene was subsequently determined.The methylation levels of OPRD1 at pos2 and pos4 in the hyperuricemia group were lower than those of the healthy control group;while the methylation level of pos4 in the Alzheimer’s disease group was higher than that of the healthy control group.Uric acid levels were negatively correlated with OPRD1 gene methylation levels.In vitro,the methylation levels at pos2,pos3 and pos4 sites of OPRD1 gene in cells with high concentration of uric acid were lower even further.The present study suggested that uric acid may affect the onset of Alzheimer’s disease by mediating the hypomethylation modification at the pos4 site of OPRD1 gene.

关 键 词：尿酸 关键酶 OPRD1基因 甲基化 阿尔茨海默病 

分 类 号：R741[医药卫生—神经病学与精神病学]