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伊朗肝硬化患者乙肝病毒株S基因中的一种新的核心启动子突变和过早终止密码子。

A new core promoter mutation and premature stop codon in the S gene in HBV strains from Iranian patients with cirrhosis.

作者信息

Veazjalali M, Norder H, Magnius L, Jazayeri S M, Alavian S M, Mokhtari-Azad T

机构信息

Virology Department, Faculty of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

J Viral Hepat. 2009 Apr;16(4):259-64. doi: 10.1111/j.1365-2893.2009.01069.x. Epub 2009 Feb 12.

Abstract

In order to define hepatitis B virus (HBV) mutational patterns in Iran, nucleotide sequences obtained from 91 patients and encompassing the precore, basal core promoter (BCP) and surface (S) regions, were compared. The patients were grouped as asymptomatic carriers, chronic active hepatitis or cirrhotic patients. Genotypes and mutations were determined by sequencing and phylogenetic analysis. All strains belonged to genotype D, and most of them to subgenotype D1. All but two strains specified ayw2, one ayw3 and one adw2 determinants. Two deletions of 8- or 20-bp were found in the X region in eight strains, six from patients with chronic active hepatitis. Eight of 21 strains from patients with cirrhosis harboured unusual mutations such as a stop codon at position 69 in the S region or a previously not described mutation in the BCP region ((1761)TC/ATTTG(1766)). All patients infected by strains with the stop codon mutation had detectable HBsAg and high viral load. The accumulation of mutations found in the BCP and S regions in HBV strains from patients with chronic active hepatitis and cirrhosis may predict disease progression in Iranian HBsAg carriers.

摘要

为了确定伊朗乙型肝炎病毒(HBV)的突变模式,对91例患者的核苷酸序列进行了比较,这些序列涵盖前核心区、核心启动子基础区(BCP)和表面(S)区。患者被分为无症状携带者、慢性活动性肝炎患者或肝硬化患者。通过测序和系统发育分析确定基因型和突变。所有菌株均属于D基因型,其中大多数属于D1亚基因型。除两株外,所有菌株均为ayw2型,一株为ayw3型,一株为adw2型。在8株菌株的X区发现了8个或20个碱基对的两个缺失,其中6株来自慢性活动性肝炎患者。21例肝硬化患者中有8株携带异常突变,如S区第69位的终止密码子或BCP区先前未描述的突变((1761)TC/ATTTG(1766))。所有感染有终止密码子突变菌株的患者均可检测到HBsAg且病毒载量高。慢性活动性肝炎和肝硬化患者的HBV菌株在BCP和S区发现的突变积累可能预示着伊朗HBsAg携带者的疾病进展。

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