干扰素受体1子多态性影响高加索人的HBeAg阴性慢性HBV感染结

StephenW

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

    Timokratis Karamitros1,2, George Papatheodoridis3,4, Eleni Dimopoulou3, Maria-Vasiliki Papageorgiou3,4, Dimitrios Paraskevis1, Gkikas Magiorkinis1,2, Vana Sypsa1 andAngelos Hatzakis1,*

Article first published online: 17 MAY 2015

DOI: 10.1111/liv.12859

© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Issue
Liver International
Liver International

Volume 35, Issue 12, pages 2506–2513, December 2015

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

* 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]

   
Keywords:

    hepatitis virus B;interferon receptor;polymorphisms;promoter

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 not only 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.

StephenW

干扰素受体1子多态性影响高加索人的HBeAg阴性慢性HBV感染结局

    Timokratis Karamitros1,2，乔治Papatheodoridis3,4，叶莱妮Dimopoulou3，玛丽亚 - 瓦西莉奇Papageorgiou3,4，迪米特里奥斯Paraskevis1，Gkikas Magiorkinis1,2，瓦纳Sypsa1 andAngelos Hatzakis1，*

文章首次在网上公布：2015年5月17日

DOI：10.1111 / liv.12859

©2015年约翰·威利父子A / S。由John Wiley＆Sons出版有限公司

问题
肝国际
肝国际

第35卷，第12期，页2506至2513年，2015年12月

    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
    动物学，牛津大学，牛津大学，英国2部
    内科，Hippokration总医院，雅典大学医学院，雅典，希腊3二部
    消化内科，Laiko总医院，雅典大学医学院，雅典，希腊4教务部

* 对应
安吉洛Hatzakis，博士，医学博士，硕士，流行病学教授，预防医学，卫生学和流行病学与医学统计学，雅典大学医学院，75 Mikras亚洲的街，GR-11527部雅典，希腊
联系电话：（30210）7462090
传真：（30210）7462190
电子邮件：[email protected]

   
关键词：

    乙肝病毒，干扰素受体;多态性;启动子

抽象
背景和目的

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状态的载体（IC）或进展到HBeAg阴性慢性乙型肝炎可能受宿主遗传图谱。不仅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还没有进行评估。我们研究的INFAR1子多态性的关联与慢性HBV感染的183个连续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，我们进行三个单核苷酸多态性分型（单核苷酸多态性-568G / C，-408C / T，-3℃/ T）和一个可变数目串联重复INFR1启动子序列中[VNTR -77（GT）N]。
结果

检查的遗传多态性发现与HBeAg阴性慢性乙型肝炎患者的阶段有关。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，由于SNP -568G / C和VNTR -77（GT）n的局部联动，我们发现，联基因型-77（GT）N≤8 /≤8_-568GC和-77（GT）N≤8 /≤ 8_-568CC检测到更加频繁的IC中（OR = 11.69，P = 0.005和OR = 7.56，P = 0.001对-77（GT）的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。