Department of Liver Diseases, No. 3 Hospital of Zhenjiang, Zhenjiang, Jiangsu, China.
Braz J Infect Dis. 2012 May-Jun;16(3):250-5.
This study aimed to determine the natural prevalence of variants of tyrosine-methionine-aspartic acid-aspartic acid (YMDD) motif in patients with chronic hepatitis B (CHB), and to explore its relation with demographic and clinical features, hepatitis B virus (HBV) genotypes, and HBV DNA levels.
A total of 1,042 antiviral treatment naïve CHB patients (including with lamivudine [LAM]) in the past year were recruited from outpatient and inpatient departments of six centers from December 2008 to June 2010. YMDD variants were analyzed using the HBV drug resistance line probe assay (Inno-Lipa HBV-DR). HBV genotypes were detected with polymerase chain reaction (PCR) microcosmic nucleic acid cross-ELISA, and HBV deoxyribonucleic acid (DNA) was quantitated with real-time PCR. All serum samples underwent tests for HBV, HCV, and HDV with ELISA.
YMDD variants were detected in 23.3% (243/1042) of CHB patients. YMDD mutation was accompanied by L180M mutation in 154 (76.9%) patients. Both wild-type HBV and YMDD variant HBV were present in 231 of 243 patients. Interestingly, 12 patients had only YIDD and/or YVDD variants without wild YMDD motif. In addition, 27.2% (98/359) of HbeAg-positive patients had YMDD mutations, which was higher than that in HbeAg-negative patients (21.2%, 145/683). The incidence of YMDD varied among patients with different HBV genotypes, but the difference was not significant. Moreover, the incidence of YMDD in patients with high HBV DNA level was significantly higher than that in those with low HBV DNA level.
Mutation of YMDD motif was detectable at a high rate in CHB patients in this study. The incidence of YMDD may be correlated with HBeAg and HBV DNA level.
本研究旨在确定慢性乙型肝炎（CHB）患者中酪氨酸-蛋氨酸-天冬氨酸-天冬氨酸（YMDD）基序变异的自然流行率，并探讨其与人口统计学和临床特征、乙型肝炎病毒（HBV）基因型和 HBV DNA 水平的关系。
本研究共纳入 2008 年 12 月至 2010 年 6 月来自 6 家中心门诊和住院部的 1042 例过去 1 年内接受抗病毒治疗的 CHB 患者（包括拉米夫定[LAM]）。采用 HBV 耐药株线性探针分析（Inno-Lipa HBV-DR）检测 YMDD 变异。采用聚合酶链反应（PCR）微核酸交叉酶联免疫吸附试验检测 HBV 基因型，实时 PCR 定量检测 HBV 脱氧核糖核酸（DNA）。所有血清样本均采用 ELISA 法检测 HBV、HCV 和 HDV。
在 1042 例 CHB 患者中，检测到 23.3%（243/1042）存在 YMDD 变异。YMDD 突变伴有 154 例（76.9%）患者的 L180M 突变。在 243 例患者中，231 例同时存在野生型 HBV 和 YMDD 变异型 HBV。有趣的是，12 例患者仅存在 YIDD 和/或 YVDD 变异，而无野生 YMDD 基序。此外，HBeAg 阳性患者中 YMDD 突变的发生率为 27.2%（98/359），高于 HBeAg 阴性患者（21.2%，145/683）。不同 HBV 基因型患者的 YMDD 发生率不同，但差异无统计学意义。此外，HBV DNA 水平较高的患者 YMDD 发生率明显高于 HBV DNA 水平较低的患者。
本研究中 CHB 患者 YMDD 基序突变的检出率较高。YMDD 的发生率可能与 HBeAg 和 HBV DNA 水平相关。
