APTR基因DNA甲基化及mRNA表达水平与HBV感染的相关性研究  

Correlation of mRNA expression levels and DNA methylation levels of APTR with HBV infection

作　　者：钱舒然 龚明 谭婧文 何越峰 李晖[1] Qian Shuran;Gong Ming;Tan Jingwen;He Yuefeng;Li Hui(Department of Hepatology,Affiliated Hospital of Yunnan University,Kunming 650021,China;School of Public Health Kunming Medical University,Kunming 650050,China)

机构地区：[1]云南大学附属医院肝病科,昆明650021 [2]昆明医科大学公共卫生学院,650050

出　　处：《中华临床感染病杂志》2021年第6期427-433,共7页Chinese Journal of Clinical Infectious Diseases

基　　金：云南省医疗卫生单位内设研究机构科研项目(2018NS0004)。

摘　　要：目的探讨Alu介导的p21转录调节子(Alu-mediated p21 transcriptional regulator, APTR)基因的DNA甲基化及mRNA表达水平与HBV感染的相关性。方法选择2019年1月至12月云南大学附属医院收治的100例HBV感染者为研究对象, 其中慢性乙型肝炎(Chronic hepatitis B, CHB)组50例, 乙型肝炎病毒无症状携带者(Asymptomatic carries of hepatitis B virus, ASC)组50例。另选同期体检者50名作为健康对照组。采用甲基化敏感的高分辨率熔解曲线(Methylation-sensitive high-resolution melting, MS-HRM)检测APTR基因的DNA甲基化程度;采用实时荧光定量聚合酶链反应(Real-time quantitative polymerase chain reaction, qRT-PCR)检测所有研究对象外周血白细胞内APTR基因的mRNA表达水平。相关性分析采用Pearson相关或Spearman秩相关。结果 CHB组、ASC组以及健康对照组的APTR基因甲基化水平分别为[12.02(9.30, 23.32)]%、[10.02(8.46, 17.44)]%和8.86[(7.82, 11.57)]%, 差异具有统计学意义(χ^(2)=13.360, P<0.01), CHB组的APTR基因甲基化水平高于健康对照组(Z=31.480, P<0.01)。CHB组、ASC组以及健康对照组的APTR基因mRNA表达水平分别为(2.38±1.41)、(5.78±2.78)和(5.70±2.66), 差异存在统计学意义(F=33.720, P<0.01), CHB组的APTR基因mRNA表达水平低于健康对照组和ASC组, 差异有统计学意义(t=7.808和7.724, P值均<0.01)。相关性分析结果显示, 所有研究对象中APTR基因的甲基化水平与mRNA表达量呈负相关(r=-0.305, P<0.01);HBV感染者中APTR基因的甲基化水平与HBsAg水平呈正相关(r=0.231, P<0.05), APTR基因mRNA表达量与HBsAg水平呈负相关(r=-0.245, P<0.05)。结论 APTR基因DNA甲基化及mRNA表达水平在不同时期HBV感染者中存在差异, 提示其可能参与了HBV感染的免疫调控。Objective To investigate the correlation of mRNA expression levels and DNA methylation levels of Alu-mediated p21 transcriptional regulator(APTR)with hepatitis B virus infection.Methods One hundred patients with HBV infection admitted in Affiliated Hospital of Yunnan University during January to December 2019 were enrolled in the study,including 50 patients with chronic hepatitis B(CHB group)and 50 asymptomatic HBV carriers(ASC group);and 50 healthy subjects were also enrolled as the healthy control group.The DNA methylation levels of APTR gene were detected by methylation-sensitive high-resolution melting(MS-HRM);the expression levels of APTR mRNA were detected by fluorescence real-time quantitative PCR(qRT-PCR).Pearson correlation or Spearman rank correlation was used for correlation analysis.Results There were significant differences in the APTR DNA methylation levels among the CHB,ASC and healthy control groups{[12.02(9.30,23.32)]%,[10.02(8.46,17.44)]%and[8.86(7.82,11.57)]%,χ^(2)=13.360,P<0.01}.The APTR DNA methylation levels were significantly higher in CHB group than those in healthy control group(Z=31.480,P<0.01).There were significant differences in the APTR mRNA expression levels among CHB,ASC and healthy control groups(2.38±1.41,5.78±2.78 and 5.70±2.66,F=33.720,P<0.01).The APTR mRNA expression levels were significantly lower in CHB group than those in healthy control and ASC groups(t=7.808 and 7.724,both P<0.01).Correlation analysis showed that the DNA methylation level of APTR gene was negatively correlated with mRNA expression levels(r=-0.305,P<0.01)in all subjects.The DNA methylation level of APTR gene was positively correlated with HBsAg level(r=0.231,P=0.022),and the mRNA expression level was negatively correlated with HBsAg level(r=-0.245,P=0.014)in patients with HBV infection.Conclusion There are differences in DNA methylation and mRNA expression of APTR gene in different stages of HBV infection,suggesting that APTR gene may be involved in the immune regulation of HBV infection.

关 键 词：乙型肝炎病毒 APTR基因 长链非编码RNA 

分 类 号：R512.62[医药卫生—内科学]