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B和T淋巴细胞衰减因子基因变异对慢性乙型肝炎病毒感染易感性的影响。

The Influence of B and T Lymphocyte Attenuator Genetic Variants on Susceptibility to Chronic Hepatitis B Virus Infection.

作者信息

Tang Jie, Fei Jiaqian, Gu Chunxia, Liu Weixia, Li Minwei, Zhou Cheng

机构信息

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Department of Disease Control and Prevention, Zhejiang Qingchun Hospital, Hangzhou, China.

出版信息

Cell Physiol Biochem. 2018;45(6):2540-2547. doi: 10.1159/000488272. Epub 2018 Mar 16.

Abstract

BACKGROUND/AIMS: B and T lymphocyte attenuator (BTLA) is an immune inhibitory receptor involved in the pathogenesis of chronic viral infections. Little is known about the effects of BTLA gene polymorphisms on chronic hepatitis B virus (HBV) infections. In this study, we investigated whether the polymorphisms of BTLA are associated with the progression of chronic HBV infection.

METHODS

A total of 382 chronic HBV carriers and 170 healthy individuals in the same region were recruited for this study. The chronic HBV carriers were divided into three groups: asymptomatic HBV carriers (ASC), moderate chronic hepatitis B group (MCHB), and severe chronic hepatitis B group (SCHB). Two BTLA functional single nucleotide polymorphisms (SNPs; rs76844316 and rs9288952) were genotyped by polymerase chain reaction and sequenced directly.

RESULTS

The results showed that the frequency of the G allele of rs76844316 was significantly lower in the SCHB group than in the other three groups. Subjects bearing at least one G allele (TG or GG genotype) at rs76844316 had decreased susceptibility to severe chronic hepatitis B compared with those bearing the TT genotype. Haplotype analysis of the two SNPs revealed that the frequency of the G-G haplotype was significantly lower in SCHB patients than in controls. Moreover, in the SCHB group, patients carrying the G allele of rs76844316 tended to have lower ALT levels than those without it.

CONCLUSION

Our findings suggest that the genetic variants of rs76844316 in BTLA influence the susceptibility to severe chronic hepatitis B and might play a protective role against the progression of chronic hepatitis B.

摘要

背景/目的:B和T淋巴细胞衰减器(BTLA)是一种参与慢性病毒感染发病机制的免疫抑制受体。关于BTLA基因多态性对慢性乙型肝炎病毒(HBV)感染的影响知之甚少。在本研究中,我们调查了BTLA的多态性是否与慢性HBV感染的进展相关。

方法

本研究共招募了同一地区的382例慢性HBV携带者和170名健康个体。慢性HBV携带者分为三组:无症状HBV携带者(ASC)、中度慢性乙型肝炎组(MCHB)和重度慢性乙型肝炎组(SCHB)。通过聚合酶链反应对两个BTLA功能性单核苷酸多态性(SNP;rs76844316和rs9288952)进行基因分型并直接测序。

结果

结果显示,rs76844316的G等位基因频率在SCHB组中显著低于其他三组。与携带TT基因型的个体相比,rs76844316至少携带一个G等位基因(TG或GG基因型)的个体对重度慢性乙型肝炎的易感性降低。对这两个SNP的单倍型分析显示,SCHB患者中G-G单倍型的频率显著低于对照组。此外,在SCHB组中,携带rs76844316的G等位基因的患者ALT水平往往低于未携带该等位基因的患者。

结论

我们的研究结果表明,BTLA中rs76844316的基因变异影响对重度慢性乙型肝炎的易感性,并可能对慢性乙型肝炎的进展起到保护作用。

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