干扰素- δ 3基因多态性变异rs4803217和rs12980275，血液透析患者对HBV疫苗的反应性和HBV和HCV暴露的结局

IF 0.3 4区医学 Q4 GASTROENTEROLOGY & HEPATOLOGY

Hepatitis Monthly Pub Date : 2021-03-31 DOI:10.5812/HEPATMON.100210

A. Grzegorzewska, W. Marcinkowski, W. Warchoł, A. Mostowska, Paweł P. Jagodziński

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引用次数: 1

摘要

背景:在非尿毒症人群中，IFNL3信使RNA 3 '非翻译区的rs4803217或IFNL3下游的rs12980275与HCV和HBV的自发或治疗性清除有关，rs12980275与血浆IFN- 3水平相关。此外，rs12980275与血液透析患者慢性丙型肝炎抗病毒治疗后的持续病毒学反应相关。目的:研究IFNL3多态性rs4803217和rs12980275与血液透析个体对HBV疫苗的反应性以及HBV和HCV暴露的自然后果的相关性。方法:接种疫苗或自然暴露后产生抗hbs保护性滴度≥10 IU/L的能力得到认可。采用高分辨率熔化曲线法分析1,337例血液透析患者的IFNL3 rs4803217 (G>T)和rs12980275 (A>G)遗传变异。采用ELISA法测定188例患者血浆IFN-λ3。生存率分析采用Kaplan-Meier法。结果:测试的多态性与HBV疫苗接种或暴露和自我限制HBV暴露后产生保护性抗hbs滴度的能力无关。自然HCV清除率与IFNL3 rs4803217 GG基因型(OR: 3.036, 95% CI: 1.544 - 5.969, P = 0.001)和包含至少两个以上频繁等位基因但不包含任何IFNL3/IFNL4遗传变异等位基因的单倍型相关(P < 0.05)。血浆IFN-λ3水平不受IFNL3 rs4803217和rs12980275的直接影响，但与HBV/HCV血清标志物存在差异(P = 0.00005)，且与抗hbs滴度密切相关(r = 0.537, P = 4.15E-16)。两种测试的多态性与血液透析患者的生存无显著相关。结论:基因分型IFNL3 rs4803217可能有利于HCV自然清除的预后，但不能预测HBV暴露的自限性、对HBV疫苗的反应性或血液透析患者的死亡率。

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Interferon-λ3 Gene Polymorphic Variants, rs4803217 and rs12980275, Responsiveness to HBV Vaccine and Outcome of HBV and HCV Exposure in Hemodialyzed Patients

Background: In non-uremic populations, rs4803217 in the IFNL3 messenger RNA 3’ untranslated region or rs12980275 downstream of IFNL3 is connected with the spontaneous or therapeutic clearance of HCV and HBV, and rs12980275 is correlated with plasma IFN-λ3 levels. Moreover, rs12980275 is associated with the sustained virological response following antiviral therapy of chronic hepatitis C in hemodialysis patients. Objectives: We investigated IFNL3 polymorphisms, rs4803217 and rs12980275, for association with responsiveness to HBV vaccine and natural consequences of HBV and HCV exposure among hemodialyzed individuals. Methods: The capacity to produce protective anti-HBs titers was recognized if they were ≥ 10 IU/L after vaccination or natural exposure. The IFNL3 rs4803217 (G>T) and rs12980275 (A>G) genetic variants were analyzed using a high-resolution melting curve method in 1,337 hemodialysis subjects. Plasma IFN-λ3 was determined in 188 individuals using ELISA. The Kaplan-Meier method was applied for the analysis of survival probability. Results: The tested polymorphisms did not show associations with the capacity to generate protective anti-HBs titers after HBV vaccination or exposition and self-limitation of HBV exposure. Natural HCV clearance was connected with the IFNL3 rs4803217 GG genotype (OR: 3.036, 95% CI: 1.544 - 5.969, P = 0.001) and haplotypes comprising at least two more frequent alleles but without any variant allele of IFNL3/IFNL4 genetic variants (P < 0.05). Plasma IFN-λ3 levels were not directly influenced by IFNL3 rs4803217 and rs12980275, but differed concerning HBV/HCV serum markers (P = 0.00005) and firmly correlated with anti-HBs titers (r = 0.537, P = 4.15E-16). Both tested polymorphisms were not significantly associated with the survival of hemodialysis patients. Conclusions: Genotyping IFNL3 rs4803217 may be advantageous in the prognosis of natural HCV clearance but does not predict the self-limitation of HBV exposure, responsiveness to HBV vaccine, or hemodialysis patients’ mortality.

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来源期刊

Hepatitis Monthly 医学-胃肠肝病学

CiteScore

1.50

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： Hepatitis Monthly is a clinical journal which is informative to all practitioners like gastroenterologists, hepatologists and infectious disease specialists and internists. This authoritative clinical journal was founded by Professor Seyed-Moayed Alavian in 2002. The Journal context is devoted to the particular compilation of the latest worldwide and interdisciplinary approach and findings including original manuscripts, meta-analyses and reviews, health economic papers, debates and consensus statements of the clinical relevance of hepatological field especially liver diseases. In addition, consensus evidential reports not only highlight the new observations, original research, and results accompanied by innovative treatments and all the other relevant topics but also include highlighting disease mechanisms or important clinical observations and letters on articles published in the journal.