乙型肝炎病毒增强子I／X基因启动子变异与HBV慢性感染疾病谱的关系  

Hepatitis B virus （HBV） mutation in Enhancer I （HBV Enh I ） / X-promoter and the relationship between chronic HBV-related disease spectrum

作　　者：邓浩辉[1] 关玉娟[1] 雷春亮[1] 许敏[1] 胡凤玉[1] 程杰[1] 李粤平[1] 

机构地区：[1]广州市第八人民医院肝病科,510060

出　　处：《中华实验和临床病毒学杂志》2012年第1期25-27,共3页Chinese Journal of Experimental and Clinical Virology

摘　　要：目的探讨乙型肝炎病毒增强子I（HBVEnhI）／X基因启动子变异与乙型肝炎病毒慢性化感染疾病谱的关系。方法随机收集275例HBV感染者的血清标本，包括慢性乙型肝炎（CHB）100例，肝硬化（LC）74例，肝细胞癌（HCC）101例。以入选病例的基因型为分组，采用半巢式PCR的方法扩增HBVEnhI／X基因启动子并测序，测序结果与HBV参照序列比对，确定变异位点，使用x^2检验和多变量logistic回归进行数据分析。结果①HBV基因分型结果：HBVB基因型患者158例（61．48％），包括CHB70例，LC36例，HCC52例；HBVC基因型患者117例（38．52％），包括CHB30例，LC38例，HCC49例。②HBVB基因型A1123Y变异在LC组明显高于CHB组（30．56％vs．8．58％，x^2=8．533，P=0．005，A=4．693，95％CI[1．567～14．056]），HCC组明显高于CHB组（28．85％vs．8．58％，x^2=8．607，P=0．003，OR=4．324，95％CI[1．544～12．109]）；A1317G变异在HCC组明显高于CHB组（30．77％VS．7．14％，x^2=11．687，P=0．001，A=5．778，95％CI[1．955—17．076]）。HBVC基因型T1323C变异在HCC组明显高于CHB组（30．61％vs．6．67％，x^2=6．318，P=0．012，A=6．176，95％CI[1．301-29．331]）。③多变量logistic回归分析发现A1317G（A=5．706，95％CI[1．770～18．837]，P=0．004）和T1323C（A=5．810，95％CI[1．114～30．306]，P=0．037）变异是HCC发生的独立危险因素。结论乙型肝炎病毒增强子I／X基因启动子突变与肝硬化、肝癌的发生有关，对变异位点的检测有助于预测肝硬化和肝癌的发生。Objective To investigate the hepatitis B virus （HBV） mutation in the Enhancer I （HBV Enh I ） / X-promoter and to analysis the relationship between chronic HBV-related disease spectrum. Methods 275 patients were enrolled in this study, including 100 cases of chronic hepatitis B （CHB）, 74 cases of liver cirrhosis （LC） , 101 cases of hepatocellular carcinoma （HCC）, grouping by different HBV genotypes, using semi-nested PCR amplification of HBV Enh I / X-promoter and sequencing DNA, the mutations were determined by alignment to HBV reference sequence, the data was compared by X2 test and analyzed by multivariate logistic regression. Results （1）Genotyping results： 61.48% （158/257） were infected with HBV genotype B, including 70 cases of CHB, 36 cases of LC and 52 cases of HCC; 38.52% （117/257） were infected with HBV genotype C, including 30 cases of CHB, 38 cases of LC and 49 cases of HCC. （2）In the patients were infected with HBV genotype B, Al123Y mutation in LC was significantly higher than in CHB（30.56% vs. 8.58% ,X2 =8. 533 ,P =0. 005 ,A =4. 693,95% CI[ 1. 567 - 14. 056]）,HCC was significantly higher than in CHB（28.85% vs. 8.58%,X2 =8.607,P=0.003 , A = 4. 324,95% CI [ 1. 544 - 12. 109 ] ） ; A1317G mutation in HCC was significantly higher than in CHB （30.77% vs. 7.14% , x2 = 11. 687, P = 0. 001 ,A = 5. 778,95% CI[ 1. 955 - 17,076 ] ）. In the patients were infected with HBV genotype C, T1323C mutation in HCC was significantly higher than in CHB （30. 61% vs. 6.67% ,X2 = 6. 318, P = 0.012, A = 6. 176,95% CI [ 1. 301 - 29. 331 ] ）. （3） Multivariate regression analyses showed that A1317G（OR =5.706,95% CI[1.770 - 18. 837],P =0.004） and T1323C （A = 5. 810,95% CI[ 1. 114- 30. 306] ,P = 0. 037） mutation were risk factors for HCC. Conclusion HBV Enh I / X-promoter mutations were associated with the development of LC and HCC, the mutations can help to predict the occurrence of LC and HCC.

关 键 词：肝炎病毒 乙型 增强子元件(遗传学) 突变 

分 类 号：R51[医药卫生—内科学]