中国人群中IPS1基因多态性与聚乙二醇干扰素治疗HBeAg阳性慢性乙型肝炎疗效的相关性

Association of IPS1 polymorphisms with peginterferon efficacy in chronic hepatitis B with HBeAg-positive in the Chinese population.

作者信息

Wang Hui, Wu Haiqing, Bao Shisan, Xiang Xiaogang, Zhao Gangde, Liu Kehui, Li Fengdi, Xu Yumin, An Baoyan, Zhou Huijuan, Lu Jie, Xie Qing

机构信息

Department of Infectious Diseases, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Department of Infectious Diseases, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Cardiology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.

出版信息

Infect Genet Evol. 2015 Apr;31:161-8. doi: 10.1016/j.meegid.2015.01.013. Epub 2015 Jan 29.

DOI:10.1016/j.meegid.2015.01.013

PMID:25640825

Abstract

AIMS

To investigate whether IPS1 polymorphisms affect peginterferon alpha (PEG-IFN) efficacy in chronic hepatitis B (CHB) patients using a tag- single nucleotide polymorphism (SNP) approach.

METHODS

A total of 212 hepatitis B e antigen (HBeAg)-positive patients treated with a 48weeks of PEG-IFN monotherapy were enrolled initially and 127 patients were followed for 48weeks posttreatment. Genotype analysis was performed for 10 tag-SNPs in IPS1.

RESULTS

The end of virological response (EVR) rate was 45.8% (97/212) and the sustained virological response (SVR) rate was 45.7% (58/127). Meanwhile, 35.4% (75/212) achieved HBeAg seroconversion at the end of treatment. In a multivariate analysis, the rs2464 CC genotype was independently associated with EVR (OR 2.21, 95% CI 1.23-3.98, P=0.008) and SVR (OR 2.34, 95% CI 1.05-5.20, P=0.037) after adjustment for sex, age, HBV genotype, baseline levels of HBV DNA and ALT. Meanwhile, rs2464 CC genotype were also independently associated with decline of HBsAg levels below 1500IU/mL at 12weeks of treatment (OR 2.52, 95% CI 1.01-6.29, P=0.047). Furthermore, three SNPs were found to be independently associated with HBeAg seroconversion at the end of treatment. (1) The rs2326369 CC genotype was independently associated with no HBeAg seroconversion (OR 0.52, 95% CI 0.29-0.95, P=0.034); (2) The rs6515831 TT genotype was independently associated with HBeAg seroconversion (OR 2.11, 95% CI 1.14-3.90, P=0.017); (3) The rs2464 CC genotype was independently associated with HBeAg seroconversion (OR 2.36, 95% CI 1.26-4.42, P=0.007).

CONCLUSIONS

Polymorphisms in IPS1 are independently associated with treatment response to PEG-IFN among Chinese HBeAg-positive CHB patients.

摘要

目的

采用标签单核苷酸多态性（SNP）方法，研究IPS1基因多态性是否影响慢性乙型肝炎（CHB）患者聚乙二醇干扰素α（PEG-IFN）的疗效。

方法

最初纳入212例接受48周PEG-IFN单药治疗的乙肝e抗原（HBeAg）阳性患者，其中127例患者在治疗后随访48周。对IPS1基因中的10个标签SNP进行基因分型分析。

结果

病毒学应答结束（EVR）率为45.8%（97/212），持续病毒学应答（SVR）率为45.7%（58/127）。同时，35.4%（75/212）的患者在治疗结束时实现了HBeAg血清学转换。在多因素分析中，校正性别、年龄、HBV基因型、HBV DNA和ALT基线水平后，rs2464 CC基因型与EVR（比值比2.21，95%可信区间1.23-3.98，P=0.008）和SVR（比值比2.34，95%可信区间1.05-5.20，P=0.037）独立相关。同时rs2464 CC基因型也与治疗12周时HBsAg水平降至1500IU/mL以下独立相关（比值比2.52，95%可信区间1.01-6.29，P=0.047）。此外，发现3个SNP与治疗结束时HBeAg血清学转换独立相关。（1） rs2326369 CC基因型与未发生HBeAg血清学转换独立相关（比值比0.52，95%可信区间0.29-0.95，P=0.034）；（2） rs6515831 TT基因型与HBeAg血清学转换独立相关（比值比2.11，95%可信区间1.14-3.90，P=0.017）；（3） rs2464 CC基因型与HBeAg血清学转换独立相关（比值比2.36，95%可信区间1.26-4.42，P=0.007）。