HBV S基因变异与临床疾病的关系

The correlationship between heptatitis B surface antigen gene mutations and clinical diseases

目的探讨泉州地区乙型肝炎病毒(HBV)慢性感染者HBVS基因变异与临床疾病的关系。方法采用PCR产物直接测序技术对43例慢性HBV感染者的HBVS区进行序列测定及分析。结果 43例慢性HBV感染者中共检出基因B型29例(29/43,67.44%),C型14例(14/43,32.56%);血清学分型adw型28例(28/43,65.12%),adr型14例(14/43,32.56%),ayw型1例(1/43,0.02%)。43例慢性HBV感染者共检出HBsAg氨基酸(aa)变异位点32个,较常见的aa变异位点为sY200F、sM213I、sI126T和sF85C,这些变异位点多见于肝功能衰竭患者。HBV主要亲水区(MHR)共检出aa变异19例(19/43,44.19%),aa替换位点12个。MHR区最常见的变异位点为aa126(7/23,30.43%),其次为aa140(3/23,13.04%)。基因B型患者中sT126I/A变异2例(2/29,6.90%),基因C型患者中sI126T变异5例(5/14,35.71%),基因C型患者中aa126变异率显著高于基因B型(χ2=5.753,P<0.05)。肝功能衰竭患者aa126变异率为26.67%(4/15),高于慢性乙型肝炎患者10.71%(3/28),但差异无统计学意义(χ2=1.824,P>0.05)。肝功能衰竭患者HBVS基因变异率在"a"决定簇上显著高于慢性乙型肝炎(χ2=4.268,P<0.05)。结论泉州地区HBV基因型(血清型)以B型(adw)为主,其次为C型(adr)。部分HBVS区基因变异与HBV基因型的异质性有关,可能与严重肝病有一定的相关性。

Objective To investigate the correlationship between heptatitis B surface antigen gene mutations and clinical diseases in patients with chronic hepatitis B in Quanzhou area. Methods Surface gene region of 43 patients with chronic HBV infection was amplified by PCR and mutations were analyzed after sequencing. Results Among 43 chronic HBV infected patients, the distributions of genetypes were B （29/43, 67.44%） and C （14/43, 32.56%）, while that of subtypes were adw （28/43, 65.12%）, adr （14/43, 32.56%） and ayw （1/43, 0.02%）, respectively. Total of amino acid 32 （aa） mutations of hepatitis B surface antigen （HBsAg） were observed in these patients. The most common aa mutations including sY200F, sM213I, sI126T and sF85C, which were usually found in patients with hepatitis failure. Nineteen （19/43, 44.19%） aa mutations and 12 substitutions were found in HBV major hydrophilic region. The mutation of aal26 was the most common （7/23, 30.43%） mutation in MHR region, and there after was aal40 （3/23, 13.04%）. sT1261/A mutation was found in 2 （2/29, 6.90%） cases with genotype B, while sI126T mutation was found in 5 （5/14, 35.71%） cases with genotype C. The mutation rate of aa126 in patients with genetype C was significantly higher than that of genetype B （x2= 5.753, P 〈 0.05）. The mutation rate of aa126 in patients with liver failure （4/15, 26.67%） was higher than that of chronic hepatitis B （3/28, 10.71%）, but with no statistical significance （x2= 1.824, P 〉 0.05）. The mutation rate of surface antigen gene in ＂a＂ determinant was higher in patients with liver failure than that of chronic hepatitis B （x2= 4.268, P 〈 0.05）. Conclusions The most common genotype of HBV in Quanzhou area are B （adw） and C （adr）. Some HBV surface antigen gene mutations were correlated with HBV genotype heterogeneity, which may be correlated with serious liver disease.