Lee A-Jin, Lee Chang Hyeong, Jeon Chang-Ho
Department of Laboratory Medicine, College of Medicine, Catholic University of Daegu, Daegu, Korea.
Department of Internal Medicine, College of Medicine, Catholic University of Daegu, Daegu, Korea.
Ann Lab Med. 2014 May;34(3):230-4. doi: 10.3343/alm.2014.34.3.230. Epub 2014 Apr 8.
Most mutations in the reverse transcriptase (RT) gene of the hepatitis B virus (HBV) are related to resistance to antiviral agents. Cross-sectional studies on the mutations of this gene are rare. Thus, we analyzed the mutation patterns of RT genes and their biochemical parameters.
From 2009 to 2012, 301 blood specimens from patients with chronic hepatitis B at Daegu Catholic University Medical Center were retrospectively analyzed for the RT gene sequence of HBV, ALT, hepatitis B e antigen (HBeAg), and HBV DNA. The mutation patterns of the RT gene were compared with the biochemical parameters.
Of the 301 patients, 100 (33.2%) had no RT gene mutations. The remaining showed the following mutation patterns: rtM204I/V (50.2%), rtL180M (39.2%), and rtA181T/V (19.6%). Combined mutations were found in 146 cases (48.5%). Of these, the combination of amino acid changes at rt180+rt204 (49.3%) was most frequently detected, followed by rt181+rt236 (11.0%) and rt173+rt180+rt204 (9.6%). In the mutated group, HBV DNA and HBeAg positive rates were significantly higher (P<0.05 for both). Phenotypic analysis showed that lamivudine resistance was most frequently detected (34.6%), followed by adefovir resistance (15.6%). Multidrug resistance was detected in 48 cases (15.9%). The adefovir-resistant group had a higher proportion of cases with HBV loads greater than 2,000 IU/mL.
We found correlations between the mutation status of the RT domain and biochemical parameters such as HBV DNA and HBeAg positive rate. The presence of RT gene mutations could therefore be utilized to predict clinical status.
乙型肝炎病毒(HBV)逆转录酶(RT)基因中的大多数突变与抗病毒药物耐药性相关。关于该基因变异的横断面研究很少。因此,我们分析了RT基因的突变模式及其生化参数。
回顾性分析2009年至2012年大邱天主教大学医学中心301例慢性乙型肝炎患者的血液标本,检测HBV的RT基因序列、丙氨酸氨基转移酶(ALT)、乙肝e抗原(HBeAg)和HBV DNA。将RT基因的突变模式与生化参数进行比较。
301例患者中,100例(33.2%)无RT基因突变。其余患者表现出以下突变模式:rtM204I/V(50.2%)、rtL180M(39.2%)和rtA181T/V(19.6%)。146例(48.5%)发现有复合突变。其中,rt180+rt204位点氨基酸变化的组合(49.3%)最为常见,其次是rt181+rt236(11.0%)和rt173+rt180+rt204(9.6%)。在突变组中,HBV DNA和HBeAg阳性率显著更高(两者P均<0.05)。表型分析显示,最常检测到拉米夫定耐药(34.6%),其次是阿德福韦耐药(15.6%)。48例(15.9%)检测到多药耐药。阿德福韦耐药组中HBV载量大于2000 IU/mL的病例比例更高。
我们发现RT结构域的突变状态与HBV DNA和HBeAg阳性率等生化参数之间存在相关性。因此,RT基因突变的存在可用于预测临床状态。