Hepatitis B virus X mutations occurring naturally associated with clinical severity of liver disease among Korean patients with chronic genotype C infection
Hepatitis B virus X mutations occurring naturally associated with clinical severity of liver disease among Korean patients with chronic genotype C infection
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DOI：
10.1002/jmv.21219
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发表时间：
2008-08-01
影响因子：
12.7
通讯作者：
Kim, Bum-Joon
中科院分区：
文献类型：
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作者：
Kim, Hyun-Ju;Park, Joo-Hee;Kim, Bum-Joon
很少有报道详细的突变频率和突变模式在整个X区域根据临床状态。本研究的目的是阐明韩国队列中X区域突变模式及其频率与临床状态之间的关系，并确定与肝病进展密切相关的特定X突变类型。通过直接测序确定了184例具有不同临床特征的患者的所有X突变。在X区域中，更严重的肝病患者，肝细胞癌（HCC）（3.6%）或肝硬化（4%）的突变率总是显著高于相应的较轻形式，慢性肝炎（2.9%）或无症状携带者（2.1%），但在HBeAg血清状态方面没有发现显着差异。发现影响六个密码子的所有五种突变类型（V5 M/L、P38 S、H94 Y、I127 T/N和K130 M和V131 I）与临床严重程度显著相关。其中V5 M/L、K130 M和V131 I两种突变型在HBeAg阴性患者中的发生率高于HBeAg阳性患者。总之，研究结果表明，X区域突变的积累有助于慢性患者的疾病进展，至少是基因型C的韩国患者。特定的突变类型似乎与严重的肝脏疾病如HCC或肝硬化更相关。特别是，在本研究中首次发现的一种新的突变类型（V5 M/L）被发现与HCC显著相关。
Few reports have detailed mutation frequencies and mutation patterns in the entire X region according to clinical status. The aims of this study were to elucidate the relationships between mutation patterns and their frequencies in the X region and clinical status in a Korean cohort and determine specific X mutation types, related closely with liver disease progression. All X mutations were determined by direct sequencing in 184 patients with different clinical features. Mutation rates in the X region in patients with more severe liver disease, hepatocellular carcinoma (HCC) (3.6%) or liver cirrhosis (4%) were always significantly higher than in patients with corresponding less severe forms, chronic hepatitis (2.9%) or asymptomatic carriers (2.1%), but no significant difference in mutation rates was found in terms of HBeAg serostatus. All five mutation types (V5M/L, P38S, H94Y, I127T/N, and K130M and V131I) affecting the six codons were found to be related significantly to clinical severity. Among these, two mutation types (V5M/L and K130M and V131I) were observed more frequently in HBeAg negative patients than in HBeAg positive patients. In conclusion, the results suggest that an accumulation of mutations in the X region contributes to disease progression in chronic patients, at least Korean patients with genotype C. Specific mutation types appears to be related more to severe liver diseases such as HCC or liver cirrhosis. In particular, a novel mutation type (V5M/L) discovered firstly during the present study was found to be associated significantly with HCC.