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Genotyping of immune-related loci associated with delayed HBeAg seroconversion in immune-active chronic hepatitis B patients.
Antiviral Research ( IF 4.5 ) Pub Date : 2020-01-28 , DOI: 10.1016/j.antiviral.2020.104719
Wen-Chun Liu , I-Chin Wu , Yen-Cheng Chiu , Kuo-Chih Tseng , Chi-Yi Chen , Hung-Chih Chiu , Pin-Nan Cheng , Ting-Tsung Chang

The progression of chronic hepatitis B (CHB) is associated with single-nucleotide polymorphisms (SNPs). In this study, we demonstrated the association between immune-related SNPs and delayed spontaneous HBeAg seroconversion in immune-active CHB patients. In addition, we investigated the impact of delayed spontaneous HBeAg seroconversion-related SNPs on HBeAg seroconversion within 3 years during antiviral treatment. We enrolled 332 CHB patients and genotyped 124 SNPs associated with HBV-infected clinical outcomes, including 32 interleukin-related genes, 62 HLA genes, 9 CD marker genes, 7 NK cell receptor genes, and 14 other genes, using ABI OpenArray as a platform. Comparing the immune-active CHB patients with delayed spontaneous HBeAg seroconversion (persistent HBeAg seropositivity, older than 40 years) to those with early inefficient HBeAg seroconversion (HBeAg seroconversion with high viremia, younger than 40 years), logistic analysis revealed that rs3820998 (TANK), rs2621377 (HLA-DOB), rs3130215 (HLA-DPB2), rs2255336 (KLRK1), and rs11614913 (MIR-196A2) were significantly associated with delayed spontaneous HBeAg seroconversion. Using multivariate analysis, we determined that high serum HBV DNA levels (OR = 1.66, 95% CI = 1.33-2.08), rs3820998 (CA, OR = 3.37, 95% CI = 1.24-9.12), rs2621377 (TC, OR = 4.96, 95% CI = 1.85-13.3), rs2255336 (TT, OR = 0.09, 95% CI = 0.01-0.86), and rs11614913 (TT, OR = 2.53, 95% CI = 1.05-6.11) were five independent risk factors for delayed spontaneous HBeAg seroconversion. After patients received nucleos(t)ide analogue treatment, rs3820998 heterozygous CA variant conversely became the only independent favorable factor for treatment-induced HBeAg seroconversion within 3 years (OR = 0.21, 95% CI = 0.06-0.78). These results indicate that distinct immune-related SNPs play a vital role in regulating HBeAg status in immune-active CHB patients with or without antiviral treatment.

中文翻译:

免疫活性慢性乙型肝炎患者中与HBeAg血清转换延迟相关的免疫相关基因座的基因分型。

慢性乙型肝炎(CHB)的进展与单核苷酸多态性(SNP)相关。在这项研究中,我们证明了具有免疫活性的CHB患者中免疫相关的SNP与延迟的自发性HBeAg血清转化之间的关联。此外,我们调查了抗病毒治疗期间3年内延迟的自发性HBeAg血清转化相关SNP对HBeAg血清转化的影响。我们使用ABI OpenArray作为平台,招募了332名CHB患者,并对与HBV感染的临床结果相关的124个SNP进行了基因分型,包括32个白介素相关基因,62个HLA基因,9个CD标记基因,7个NK细胞受体基因和14个其他基因。 。比较具有免疫活性的CHB患者与延迟的自发性HBeAg血清转化(持续性HBeAg血清阳性,年龄大于40岁)到早期低效HBeAg血清转化的患者(HBeAg血清转化高病毒血症,小于40岁),逻辑分析显示rs3820998(TANK),rs2621377(HLA-DOB),rs3130215(HLA-DPB2),rs2255336( KLRK1)和rs11614913(MIR-196A2)与延迟的自发性HBeAg血清转换密切相关。使用多变量分析,我们确定血清HBV DNA高水平(OR = 1.66,95%CI = 1.33-2.08),rs3820998(CA,OR = 3.37,95%CI = 1.24-9.12),rs2621377(TC,OR = 4.96) ,95%CI = 1.85-13.3),rs2255336(TT,OR = 0.09,95%CI = 0.01-0.86)和rs11614913(TT,OR = 2.53,95%CI = 1.05-6.11)是以下5个独立的危险因素延迟自发性HBeAg血清转化。患者接受核苷类似物治疗后,相反,rs3820998杂合CA变异体成为3年内治疗诱导的HBeAg血清转化的唯一独立有利因素(OR = 0.21,95%CI = 0.06-0.78)。这些结果表明,在有或没有抗病毒治疗的情况下,具有免疫活性的CHB患者中,与免疫相关的SNP均起着至关重要的作用。
更新日期:2020-01-29
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