IL28B 多态性与乙型肝炎病毒感染自发清除的关系。
Association between IL28B polymorphisms and spontaneous clearance of hepatitis B virus infection.
机构信息
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
出版信息
PLoS One. 2013 Jul 17;8(7):e69166. doi: 10.1371/journal.pone.0069166. Print 2013.
BACKGROUND/AIMS: Single-nucleotide polymorphisms (SNPs) near the interleukin 28B gene (IL28B; interferon [IFN]-λ-3) are associated with outcomes of chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection treated with peginterferon (PEG-IFN) alpha-based antiviral therapy. In this study, we investigated the influence of IL28B polymorphisms on spontaneous clearance of HBV infection in a large Korean cohort.
METHODS
Between January 2007 and June 2010, a total of 208 patients with chronic HBV infection and newly diagnosed HBV-related hepatocellular carcinoma were recruited as the CC group [HBsAg(+) for >6 months, anti-HBc(+), and anti-HBs(-)]. In addition, 351 organ donors were stratified into the UE group [n = 106; HBsAg(-), anti-HBc(-), and anti-HBs(-)] or the SC group [n = 245; HBsAg(-), anti-HBc(+), and anti-HBs(+)]. The SNaPshot ddNTP Primer Extension Kit (Applied Biosystems, Foster City, CA) was used for SNP detection. Direct full sequencing of the IL28B coding region was attempted.
RESULTS
Regardless of group, rs12979860 CC was most frequently identified (85.0% in UE, 85.9% in SC, and 93.5% in CC, respectively), whereas rs12979860 TT was not identified in any group. Similarly, rs12980275 AA and rs8099917 TT were most frequently identified (≥85%) regardless of group, whereas rs12980275 GG was identified in only one subject in the SC group. In addition, rs8099917 GG was not identified. The prevalences of CC in rs12979860, AA in rs12980275, and TT in rs8099917 were significantly higher in the CC group when compared with the UE and SC group (all P<0.05). Among 19 novel SNPs in the IL28B coding region, the proportions of 6 SNPs were significantly different among the UE, SC, and CC groups (all P<0.05).
CONCLUSIONS
The SNP upstream of IL28B that has the strongest genetic association with HCV recovery has an inverse influence on HBV recovery. Additional studies are needed to understand the mechanisms of this SNP in HBV infection.
背景/目的：白细胞介素 28B 基因（IL28B；干扰素[IFN]-λ-3）附近的单核苷酸多态性（SNP）与聚乙二醇干扰素（PEG-IFN）α为基础的抗病毒治疗治疗慢性丙型肝炎病毒（HCV）和乙型肝炎病毒（HBV）感染的结局相关。本研究在一个大型韩国队列中调查了 IL28B 多态性对 HBV 感染自发清除的影响。
方法
2007 年 1 月至 2010 年 6 月期间，共招募了 208 例慢性 HBV 感染和新诊断的 HBV 相关肝细胞癌患者作为 CC 组[HBsAg(+)>6 个月，抗-HBc(+)，抗-HBs(-)]。此外，351 名器官捐献者分为 UE 组[n=106；HBsAg(-)，抗-HBc(-)，抗-HBs(-)]或 SC 组[n=245；HBsAg(-)，抗-HBc(+)，抗-HBs(+)。SNaPshot ddNTP Primer Extension Kit（Applied Biosystems，Foster City，CA）用于 SNP 检测。尝试对 IL28B 编码区进行直接全长测序。
结果
无论组如何，rs12979860 CC 是最常见的（UE 组为 85.0%，SC 组为 85.9%，CC 组为 93.5%），而任何组均未鉴定出 rs12979860 TT。同样，rs12979860 AA 和 rs8099917 TT 在无论组如何均为最常见（≥85%），而 rs12979860 GG 仅在 SC 组的一名患者中鉴定。此外，未鉴定出 rs8099917 GG。与 UE 和 SC 组相比，CC 组 rs12979860 的 CC、rs12980275 的 AA 和 rs8099917 的 TT 的流行率明显更高（均 P<0.05）。在 IL28B 编码区的 19 个新 SNP 中，UE、SC 和 CC 组之间 6 个 SNP 的比例有显著差异（均 P<0.05）。
结论
与 HCV 恢复具有最强遗传相关性的 IL28B 上游 SNP 对 HBV 恢复具有相反的影响。需要进一步研究以了解该 SNP 在 HBV 感染中的作用机制。
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