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

摘要

目的 探讨乙型肝炎病毒增强子Ⅰ (HBV Enh Ⅰ)/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HBV Enh Ⅰ/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x2检验和多变量logistic回归进行数据分析.结果 ①HBV基因分型结果:HBV B基因型患者158例(61.48％),包括CHB 70例,LC 36例,HCC 52例;HBV C基因型患者117例(38.52％),包括CHB 30例,LC 38例,HCC 49例.②HBV B基因型A1123Y变异在LC组明显高于CHB组(30.56％vs.8.58％,x2=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％,x2 =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％,x2=11.687,P=0.001,A=5.778,95％ CI[1.955～17.076]).HBV C基因型T1323C变异在HCC组明显高于CHB组(30.61％ vs.6.67％,x2 =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 ①Genotyping 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. ②In the patients were infected with HBV genotype B,A1123Y 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 C HB (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.