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印度东部人群中白细胞介素-1β及基因多态性与乙型肝炎病毒感染肝脏发病机制的关联

Association of Interleukin-1β and Gene Polymorphisms with Liver Pathogenesis in Hepatitis B Virus Infection among Eastern Indian Population.

作者信息

Biswas Avik, Panigrahi Rajesh, Pal Manisha, De Binay K, Chakrabarti Sekhar, Ghosh Mrinmoy K, Chandra Seth Bikash C, Roychowdhury Susanta, Chakravarty Runu

机构信息

ICMR Virus Unit Kolkata, ID & BG Hospital Campus, Kolkata, India.

Department of Pathology & Laboratory Medicine, Tulane University School of Medicine, New Orleans, USA.

出版信息

J Clin Exp Hepatol. 2013 Dec;3(4):281-7. doi: 10.1016/j.jceh.2013.11.006. Epub 2013 Dec 4.

DOI:10.1016/j.jceh.2013.11.006
PMID:25755515
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3940093/
Abstract

BACKGROUND

Interleukin-1β (IL-1β) is an important member of the family of the proinflammatory cytokines that modulate outcome of hepatitis B virus (HBV) infection.

OBJECTIVES

This study was designed to investigate the relationship between the polymorphic genotypes of the interleukin-1β (IL-1β) promoter region and the interleukin-1 receptor antagonist gene (IL-1RN) and disease outcome in HBV-infected individuals.

METHODS

DNA was extracted from 395 study subjects including HBV carriers with varying clinical presentations, as well as healthy controls and spontaneously recovered cases (SRC). Polymorphisms in IL-1β (at position -511) and IL-1RN (variable nucleotide tandem repeats, VNTR) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR based assay respectively.

RESULTS

Among the study subjects, different IL-1β (at position -511) (CC, CT and TT) and IL-1RN (1/1, 1/2, 2/2 and 1/3) polymorphic genotypes were found at variable proportions. Logistic regression analysis revealed, no notable difference at the level of IL-1β promoter (P = 0.244; OR = 0.78; 95% CI = 0.52-1.18) or IL-1RN genotype polymorphism (P = 0.840; OR = 1.03; 95% CI = 0.78-1.36) among the HBV carriers and controls or SRC cases. Pairwise proportion testing showed, IL-1β -511 genotype CC was significantly higher among asymptomatic carriers (ASC) in comparison with liver cirrhosis (LC) patients (P value = 0.028) and healthy control group (P-value = 0.036). IL-1RN genotype 2/2 was considerably higher in LC group than SRC as well as control group. Combinations of IL-1β (-511) and IL-1RN polymorphisms were associated with disease progression, such as CC-1/2 with ASC and TT-2/2 with LC.

CONCLUSION

IL-1β polymorphisms are found to be associated with disease severity. Different polymorphic combinations are associated with degree of disease severity. Overall this is the first report from Eastern India, which shows association of IL-1β polymorphisms with HBV-related hepatic complications.

摘要

背景

白细胞介素-1β(IL-1β)是促炎细胞因子家族的重要成员,可调节乙型肝炎病毒(HBV)感染的结果。

目的

本研究旨在调查白细胞介素-1β(IL-1β)启动子区域和白细胞介素-1受体拮抗剂基因(IL-1RN)的多态性基因型与HBV感染个体疾病结局之间的关系。

方法

从395名研究对象中提取DNA,这些研究对象包括具有不同临床表现的HBV携带者、健康对照者和自发康复病例(SRC)。分别采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和基于PCR的检测方法分析IL-1β(-511位点)和IL-1RN(可变核苷酸串联重复序列,VNTR)的多态性。

结果

在研究对象中,发现不同的IL-1β(-511位点)(CC、CT和TT)和IL-1RN(1/1、1/2、2/2和1/3)多态性基因型比例各不相同。逻辑回归分析显示,在HBV携带者与对照者或SRC病例之间,IL-1β启动子水平(P = 0.244;OR = 0.78;95% CI = 0.52 - 1.18)或IL-1RN基因型多态性(P = 0.840;OR = 1.03;95% CI = 0.78 - 1.36)无显著差异。成对比例检验显示,与肝硬化(LC)患者(P值 = 0.028)和健康对照组(P值 = 0.036)相比,无症状携带者(ASC)中IL-1β -511基因型CC显著更高。LC组中IL-1RN基因型2/2明显高于SRC组和对照组。IL-1β(-511)和IL-1RN多态性的组合与疾病进展相关,如CC-1/2与ASC相关,TT-2/2与LC相关。

结论

发现IL-1β多态性与疾病严重程度相关。不同的多态性组合与疾病严重程度相关。总体而言,这是来自印度东部的首份报告,显示IL-1β多态性与HBV相关肝脏并发症有关。

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