A missense variant in complement factor B (CFB) is a potential predictor of 24-week off-treatment response to PegIFNα therapy in Chinese HBeAg-positive chronic hepatitis B patients
A missense variant in complement factor B (CFB) is a potential predictor of 24-week off-treatment response to PegIFNα therapy in Chinese HBeAg-positive chronic hepatitis B patients
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补体因子 B (CFB) 中的错义变异是中国 HBeAg 阳性慢性乙型肝炎患者对 PegIFNα 治疗 24 周停药反应的潜在预测因子。
DOI：
10.1111/apt.15624
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发表时间：
2020-01-14
影响因子：
7.6
通讯作者：
Jiang, De-Ke
中科院分区：
文献类型：
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作者：
Chen, Haitao;Sun, Jian;Jiang, De-Ke
背景迄今为止，已发现14个单核苷酸多态性（SNPs）位点与慢性B型肝炎（CH B）相关。目的探讨B e抗原（HBeAg）阳性慢性乙型肝炎（CHB）患者的治疗反应与SNPs的关系。方法回顾性分析1623例中国汉族HBeAg阳性CHB患者（782例患者接受聚乙二醇干扰素α [PegIFN α]治疗48周加24周随访，841例患者接受核苷（酸）类似物[NUC]治疗104周），纳入4项IV期多中心随机对照试验。所有14个SNPs基因型为每个CHB患者。多基因评分（PGS）用于评估多个SNP的累积效应。评估SNPs或PGS与联合应答（CR）和B s抗原（HBsAg）丢失的相关性。结果我们发现rs 12614是补体因子B（CF B）的错义变异体，与PegIFN α治疗患者的CR显著相关，rs 12614 TT/CT基因型患者的CR率不到CC基因型患者的1/3（7.4%vs22.6%，P = 0.009）。此外，PGS整合CFB rs 12614和STAT 4 rs7574865（先前报道与对PegIFN α的应答相关）与PegIFN α治疗患者的CR（P趋势= 4.000 x 10（-4））和HBsAg丢失（P趋势= 0.010）显著相关。然而，没有一个SNP与NUCs治疗患者的治疗反应相关。结论CFB rs 12614是HBeAg阳性CHB患者对PegIFN α治疗应答的独立预测因子。整合CFB rs 12614与STAT 4 rs7574865的PGS可以有效区分对PegIFN α的应答者与无应答者。
Background To date, 14 single-nucleotide polymorphisms (SNPs) have been identified as susceptibility loci for chronic hepatitis B (CHB). Aim To investigate if these SNPs are associated with treatment response of hepatitis B e antigen (HBeAg)-positive CHB patients. Methods We performed a retrospective analysis of 1623 Han Chinese HBeAg-positive CHB patients (782 patients treated with pegylated interferon alpha [PegIFN alpha] for 48 weeks plus 24 weeks follow-up, and 841 patients treated with nucleos(t)ide analogues [NUCs] for 104 weeks) included in four phase-IV multicentre randomised controlled trials. All 14 SNPs were genotyped for each CHB patient. A polygenic score (PGS) was used to evaluate the cumulative effect of multiple SNPs. The associations of SNPs or PGS with combined response (CR) and hepatitis B s antigen (HBsAg) loss were assessed. Results We found that rs12614, a missense variant of complement factor B (CFB), was significantly associated with CR in PegIFN alpha-treated patients, and the CR rate in patients with the rs12614 TT/CT genotype was less than one-third of that in patients with the CC genotype (7.4% vs 22.6%, P = 0.009). Moreover, a PGS integrating CFB rs12614 and STAT4 rs7574865 (previously reported to be associated with response to PegIFN alpha) was significantly associated with both CR (P-trend = 4.000 x 10(-4)) and HBsAg loss (P-trend = 0.010) in PegIFN alpha-treated patients. However, none of the SNPs were associated with treatment response in NUCs-treated patients. Conclusions CFB rs12614 is an independent predictor of response to PegIFN alpha therapy in Chinese HBeAg-positive CHB patients. A PGS integrating CFB rs12614 with STAT4 rs7574865 can effectively discriminate responders to PegIFN alpha from nonresponders.