Effect of HLA-DP and IL28B gene polymorphisms on response to interferon treatment in hepatitis B e-antigen seropositive chronic hepatitis B patients
Effect of HLA-DP and IL28B gene polymorphisms on response to interferon treatment in hepatitis B e-antigen seropositive chronic hepatitis B patients
复制标题
HLA-DP和IL28B基因多态性对乙型肝炎e抗原血清阳性慢性乙型肝炎患者干扰素治疗反应的影响
DOI：
10.1111/hepr.12284
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发表时间：
2014-09-01
影响因子：
4.2
通讯作者：
Deng, Guohong
中科院分区：
文献类型：
--
作者：
Cheng, Lin;Sun, Xiaowen;Deng, Guohong
目的：大多数慢性乙型肝炎（CHB）患者对常规干扰素（IFN）或聚乙二醇化干扰素（PEG IFN）治疗没有反应的原因尚未得到正式证实。本研究的目的是探讨单核苷酸多态性（snp）与中国CHB患者对IFN-或PEG IFN治疗的反应之间的关系。方法采用MGB-TaqMan SNP基因分型方法对144例接受6-12个月IFN或PEG IFN治疗的乙型肝炎e抗原（HBeAg）血清阳性CHB患者HLA-DPA1、HLA-DPB1 （rs3077和rs9277535）和IL28B （rs12979860和rs8099917）区域的4个SNP进行基因分型。达到以下四项指标中的任何一项的患者被归类为应答者：(i) HBeAg的丧失；（ii）抗乙肝病毒血清转化；（三）乙型肝炎病毒（HBV） DNA水平被抑制到基线的3log以下；丙氨酸转氨酶正常化。结果通过治疗6个月和治疗后6个月的多因素分析，结果显示rs3077-GG基因型与较高的HBeAg损失率和抗- hbe血清转化率独立相关，rs9277535-GG基因型与HBV DNA水平下降独立相关。然而，我们没有观察到IL28B附近的SNP与IFN-或PEG IFN治疗的反应之间的显著关联。结论本研究提示HLA-DPA1和HLA-DPB1变异与接受IFN或PEG IFN治疗的HBeAg血清阳性CHB患者的HBeAg丢失、抗hbe血清转化和HBV DNA水平抑制显著相关。
AimThe reason why the majority of chronic hepatitis B (CHB) patients do not respond to conventional interferon (IFN)- or pegylated interferon (PEG IFN) treatment has not been formally demonstrated. The aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) and response to IFN- or PEG IFN therapy in Chinese patients with CHB.MethodsFour SNPs among the HLA-DPA1, HLA-DPB1 (rs3077 and rs9277535) and IL28B (rs12979860 and rs8099917) regions were genotyped using the MGB-TaqMan SNP genotyping assay in 144 hepatitis B e-antigen (HBeAg) seropositive CHB patients who had received 6-12 months IFN- or PEG IFN treatment. Patients were classified as responders who achieved any of the four targets: (i) the loss of HBeAg; (ii) anti-HBe seroconversion; (iii) suppression of hepatitis B virus (HBV) DNA level to below 3log of baseline; and (iv) alanine aminotransferase normalization.ResultsBy multivariate analysis at 6 months of therapy and 6 months post-therapy, the results showed that rs3077-GG genotype was independently associated with higher HBeAg loss rate and anti-HBe seroconversion rate, and rs9277535-GG genotype was independently associated with decline of HBV DNA level. However, we did not observe the significant association between SNP near IL28B and the response to IFN- or PEG IFN treatment.ConclusionThis study suggested that HLA-DPA1 and HLA-DPB1 variants were significantly associated with HBeAg loss, anti-HBe seroconversion and HBV DNA level suppression in HBeAg seropositive CHB patients who received IFN- or PEG IFN treatment.