Li Jing, Chen Haitao, Chen Jiaxuan, Zhou Bin, Hou Jinlin, Jiang De-Ke
State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral Hepatitis Research, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, People's Republic of China.
Pharmgenomics Pers Med. 2021 Nov 23;14:1505-1515. doi: 10.2147/PGPM.S337962. eCollection 2021.
Granulysin (GNLY) is a cytotoxic granule that has been reported to have various antimicrobial activities. We evaluated the association between a missense variant in (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 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, rs7574865, rs12614, and rs28371597, which were reported to be associated with CR.
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%, = 0.003). Furthermore, a PGS integrating rs11127 and three other SNPs was significantly associated with CR in PegIFNα-treated patients ( < 0.001). However, no significant correlation was found between rs11127 and CR in NUCs-treated patients.
rs11127 is an independent biomarker for predicting the response to PegIFNα therapy in HBeAg-positive CHB patients. Furthermore, the PGS, including rs11127, provides new insights for individualized treatment in clinical practice.
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。我们评估了慢性乙型肝炎（CHB）患者中rs11127的错义变异与聚乙二醇化干扰素-α（PegIFNα）或核苷（酸）类似物（NUCs）治疗疗效之间的关联。
我们纳入了四项IV期多中心随机对照试验中的1823例乙型肝炎e抗原（HBeAg）阳性的CHB患者（954例接受PegIFNα治疗，869例接受NUCs治疗）。评估了rs11127基因型与联合应答（CR）的关联，联合应答定义为HBeAg血清学转换且乙型肝炎病毒（HBV）DNA水平<2000 IU/mL。构建了一个多基因评分（PGS）以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，即rs7574865、rs12614和rs28371597，据报道这些SNP与CR相关。
rs11127与接受PegIFNα治疗的患者的CR显著相关。rs11127 CC基因型患者的CR率高于CT或TT基因型患者（40.98%对30.34%或27.09%，P = 0.003）。此外，整合了rs11127和其他三个SNP的PGS与接受PegIFNα治疗的患者的CR显著相关（P<0.001）。然而，在接受NUCs治疗的患者中，未发现rs11127与CR之间存在显著相关性。
rs11127是预测HBeAg阳性CHB患者对PegIFNα治疗反应的独立生物标志物。此外，包括rs11127的PGS为临床实践中的个体化治疗提供了新的见解。
