干扰素受体1子多态性影响高加索人的HBeAg阴性慢性HBV感染的

StephenW

The interferon receptor-1 promoter polymorphisms affect the outcome of Caucasians with HBeAg-negative chronic HBV infection

    Timokratis Karamitros1,4, George Papatheodoridis2,3, Eleni Dimopoulou2, Maria-Vasiliki Papageorgiou2,3, Dimitrios Paraskevis1, Gkikas Magiorkinis1,4, Vana Sypsa1 andAngelos Hatzakis1,*

DOI: 10.1111/liv.12859

This article is protected by copyright. All rights reserved.

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Cover image for Vol. 35 Issue 5
Liver International

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

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Publication History
Author Information

    1    Department of Hygiene and Epidemiology and Medical Statistics, Athens University Medical School, Athens, Greece
    2    2nd Department of Internal Medicine, Hippokration General Hospital, Athens University Medical School, Athens, Greece
    3    Academic Department of Gastroenterology, Laiko General Hospital, Athens University Medical School, Athens, Greece
    4    Department of Zoology, University of Oxford, Oxford, United Kingdom

* Address correspondence:
Angelos Hatzakis, PhD, MD, MSc
Professor of Epidemiology and Preventive Medicine,
Department of Hygiene and Epidemiology and Medical Statistics, Athens University Medical School
75 Mikras Asias Street, GR-11527 Athens, Greece
Tel: (+30210)7462090
Fax: (+30210)7462190
e-mail: [email protected]

    This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/liv.12859


Keywords:

    Hepatitis Virus B;Interferon Receptorromoterolymorphisms

Abstract
Background/Aims

The outcome of HBeAg-negative chronic hepatitis B virus (HBV) patients who may remain in the inactive carrier state (IC) or progress to HBeAg-negative chronic hepatitis B may be affected by the host genetic profile. Genetic polymorphisms within the promoter but also the coding sequence of the interferon receptor 1 (INFAR1) gene have been associated with susceptibility to chronic HBV infection, but their role on the outcomes of HBeAg-negative patients has not been evaluated. We examined the association of INFAR1 promoter polymorphisms with the phase of chronic HBV infection in a demographically characterized Caucasian cohort of 183 consecutive HBeAg-negative chronic HBV patients.
Methods

Using a combination of conventional and allele-specific polymerase chain reactions, bidirectional sequencing and DNA-fragment analysis, we performed typing of three Single Nucleotide Polymorphisms (SNPs -568G/C, -408C/T, -3C/T) and one Variable Number Tandem Repeat (VNTR -77(GT)n) within the INFR1 promoter sequence.
Results

The genetic polymorphisms examined were found to be associated with the phase of HBeAg-negative chronic HBV patients. Using a multiple logistic regression model adjusting for age, gender and origin of the individuals, we found that patients with linked genotypes -408CT_-3CT were more likely to be ICs (OR=2.42 vs. CC, p=0.036). Also, given the partial linkage between SNP -568G/C and VNTR -77(GT)n, we found that linked genotypes -77(GT)n≤8/≤8_-568GC and -77(GT)n≤8/≤8_-568CC were detected more frequently among ICs (OR=11.69, p=0.005 and OR=7.56, p=0.001 vs. -77(GT)n>8/>8_-568GG, respectively).
Conclusions

These findings suggest that these genetic variations represent important factors associated with the clinical phase of HBeAg-negative chronic HBV infection.

This article is protected by copyright. All rights reserved.

StephenW

干扰素受体1子多态性影响高加索人的HBeAg阴性慢性HBV感染的结局

    Timokratis Karamitros1,4，乔治Papatheodoridis2,3，叶莱妮Dimopoulou2，玛丽亚 - 瓦西莉奇Papageorgiou2,3，迪米特里奥斯Paraskevis1，Gkikas Magiorkinis1,4，瓦纳Sypsa1 andAngelos Hatzakis1，*

DOI：10.1111 / liv.12859

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问题
封面图片卷。 35第5期
肝国际

接受第（接受，未编辑的文章，并在网上公布可引用的最终编辑和记录的排版本将出现在未来。）

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作者信息
出版物历史
作者信息

    卫生与流行病学和医学统计学，雅典大学医学院，雅典，希腊1系
    内科，Hippokration总医院，雅典大学医学院，雅典，希腊2二部
    消化内科，Laiko总医院，雅典大学医学院，雅典，希腊3教务部
    动物学，牛津大学，牛津大学，英国4部

*通讯地址：
安吉洛Hatzakis，博士，医学博士，硕士
流行病学教授预防医学，
卫生与流行病学和医学统计学，雅典大学医学院系
75 Mikras亚洲的街，GR-11527雅典，希腊
联系电话：（30210）7462090
传真：（30210）7462190
电子邮件：[email protected]

    这篇文章已被接受发表，并经过充分的同行评审，但经过审稿，排版，分页和校对过程中，这可能会导致这个版本和记录的版本之间的差异一直没有。请引用这篇文章的DOI：10.1111 / liv.12859


关键词：

    乙肝病毒;干扰素受体;启动子;多态性

抽象
背景/目的

HBeAg阴性慢性乙型肝炎病毒（HBV）的患者的结果谁可以保持在非活动载波状态（IC）或进展到HBeAg阴性慢性乙型肝炎可能受宿主遗传图谱。启动子也是干扰素受体1（INFAR1）基因的编码序列内的遗传多态性已与易感性慢性HBV感染有关，但它们对HBeAg阴性患者的预后作用尚未评估。我们研究的INFAR1子多态性的关联与慢性HBV感染的连续183例HBeAg阴性慢性乙肝患者人口统计学特征高加索人群的阶段。
方法

使用常规和等位基因特异性聚合酶链反应，双向测序和DNA片段分析的组合，我们进行了三个单核苷酸多态性分型（单核苷酸多态性-568G / C，-408C / T，-3C / T）和一个可变数目串联重复序列（VNTR -77（GT）N）的​​INFR1启动子序列之内。
结果

检查的遗传多态性发现与HBeAg阴性慢性乙肝患者的阶段有关。采用多元回归模型调整了年龄，性别和个人的出身，我们发现患者挂基因型-408CT_-3CT更可能是集成电路（OR = 2.42与CC，P = 0.036）。此外，给定的SNP -568G / C和VNTR -77（GT）之间的局部联动N，我们发现，联基因型-77（GT）n≤8/≤8_-568GC和-77（GT）n≤8/≤ 8_-568CC检出更频繁的IC间（OR = 11.69，p值= 0.005和OR = 7.56，p值= 0.001对-77（GT）N> 8 /> 8_-568GG，分别）。
结论

这些结果表明，这些遗传变异表示与HBeAg阴性慢性HBV感染者的临床阶段相关联的重要因素。

这篇文章是受版权保护的。版权所有。