A Missense Variant in Granulysin is Associated with the Efficacy of Pegylated-Interferon-Alpha Therapy in Chinese Patients with HBeAg-Positive Chronic Hepatitis B.
A Missense Variant in Granulysin is Associated with the Efficacy of Pegylated-Interferon-Alpha Therapy in Chinese Patients with HBeAg-Positive Chronic Hepatitis B.
复制标题
颗粒溶素的错义变异与聚乙二醇化干扰素-α 治疗中国 HBeAg 阳性慢性乙型肝炎患者的疗效相关
DOI：
10.2147/pgpm.s337962
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发表时间：
2021
影响因子：
1.9
通讯作者：
Jiang DK
中科院分区：
文献类型：
--
作者：
Li J;Chen H;Chen J;Zhou B;Hou J;Jiang DK
颗粒溶素 (GNLY) 是一种细胞毒性颗粒，据报道具有多种抗菌活性。我们评估了 GNLY (rs11127) 错义变异与聚乙二醇化干扰素-α (PegIFNα) 或核苷（酸）类似物 (NUC) 对慢性乙型肝炎 (CHB) 患者的治疗效果之间的关联。我们在四项 IV 期多中心随机对照试验中总共纳入了 1823 名乙型肝炎 e 抗原 (HBeAg) 阳性 CHB 患者（其中 954 名患者接受 PegIFNα 治疗，869 名患者接受 NUC 治疗）。评估了 GNLY rs11127 基因型与联合反应 (CR) 的关联，联合反应定义为 HBeAg 血清转化和乙型肝炎病毒 (HBV) DNA 水平 <2000 IU/mL。构建多基因评分（PGS）来评估多个单核苷酸多态性（SNP）的累积效应，包括rs11127和其他几个SNP，STAT4 rs7574865，CFB rs12614和CD55 rs28371597，据报道这些与CR相关。 GNLY rs11127 与接受 PegIFNα 治疗的患者的 CR 显着相关。 rs11127 CC基因型患者的CR率高于CT或TT基因型患者（40.98% vs 30.34%或27.09%，P = 0.003）。此外，整合 GNLY rs11127 和其他三个 SNP 的 PGS 与 PegIFNα 治疗患者的 CR 显着相关（P < 0.001）。然而，在 NUC 治疗的患者中，GNLY rs11127 与 CR 之间没有发现显着相关性。 GNLY rs11127 是一种独立的生物标志物，用于预测 HBeAg 阳性 CHB 患者对 PegIFNα 治疗的反应。此外，包括 GNLY rs11127 在内的 PGS 为临床实践中的个体化治疗提供了新的见解。
Granulysin (GNLY) is a cytotoxic granule that has been reported to have various antimicrobial activities. We evaluated the association between a missense variant in GNLY (rs11127) and treatment efficacy of pegylated interferon-alpha (PegIFNα) or nucleos(t)ide analogs (NUCs) in patients with chronic hepatitis B (CHB). We included a total of 1823 patients with hepatitis B e antigen (HBeAg)-positive CHB (954 patients treated with PegIFNα and 869 patients treated with NUCs) in four Phase IV multicenter randomized controlled trials. The association of the GNLY rs11127 genotype with the combined response (CR), defined as HBeAg seroconversion and hepatitis B virus (HBV) DNA level <2000 IU/mL was evaluated. A polygenic score (PGS) was constructed to evaluate the cumulative effect of multiple single-nucleotide polymorphisms (SNPs), including rs11127 and several other SNPs, STAT4 rs7574865, CFB rs12614, and CD55 rs28371597, which were reported to be associated with CR. GNLY rs11127 was significantly associated with CR in patients treated with PegIFNα. The CR rate in patients with the rs11127 CC genotype was higher than that with the CT or TT genotype (40.98% vs 30.34% or 27.09%, P = 0.003). Furthermore, a PGS integrating GNLY rs11127 and three other SNPs was significantly associated with CR in PegIFNα-treated patients (P < 0.001). However, no significant correlation was found between GNLY rs11127 and CR in NUCs-treated patients. GNLY rs11127 is an independent biomarker for predicting the response to PegIFNα therapy in HBeAg-positive CHB patients. Furthermore, the PGS, including GNLY rs11127, provides new insights for individualized treatment in clinical practice.