表面抗原和抗体双阳性慢性乙型肝炎病毒感染者病毒S基因的变异分析

S gene mutations in HBsAg/HBsAb double positive chronic hepatitis B patients

目的了解HBsAg和抗HBs双阳性慢性HBV感染者的S基因变异情况。方法分别对8例HBsAg和抗-HBs双阳性（实验组）及9例HBsAg阳性、抗-HBs阴性慢性}tBV感染者（对照组）的S基因进行PcR扩增并测序，将测序结果进行对比分析。基因型和血清型分布比较、主要亲水区变异位点数比较采用Fisher’s精确检验，核苷酸和氨基酸序列的同源性比较采用t检验。结果感染HBV的基因型分布：实验组为B型2例、C型6例，对照组为B型6例、C型3例，两组问差异无统计学意义（P〉0．05）；血清型分布：实验组为adw2例、adr5例、ayr1例，对照组为adw6例、adr3例，两组问差异无统计学意义（P〉0．05）。实验组和对照组HBV前S1区的核昔酸替换率（2．29％比1．8％）和氨基酸替换率（2．66％比1．59％）差异无统计学意义（t值分别为1．56和1．39，P值均〉0．05）；前S2区的核苷酸替换率（1．74％比0．91％）差异有统计学意义（t=4．68，P〈0．01），氨基酸替换率（3．18％比2．05％）差异无统计学意义（t=1．85，P〉0．05）；S区的核苷酸替换率（2．13％比0．81％）和氨基酸替换率（4．37％比1．52％）差异有统计学意义（t值分别为6.00和5.32，P值均〈0．01）。主要亲水区内外均存在氨基酸的替换，“a”决定簇变异相对较高（P〈0．05）。结论HBsAg和抗-HBs双阳性慢性HBV感染者的S基因变异率相对较高。

Objective To investigate S gene mutations in HBsAg/HBsAb double positive chronic hepatitis B patients. Methods HBV S gene from 8 patients （Group A） with HBsAg （＋）/HBsAb （＋） and 9 patients （Group B） with HBsAg （＋）/HBsAb （-）was amplified by polymerase chain reaction （PCR） and sequencing. Both the distribution of genotype and serotype and the rate of MHR region were compared by Fisher＇s exact test. The mutation rate of both the DNA level and amino acid level was compared by t test. Results No significant difference in distribution of genotypes was found between the two groups （P = 0.153）. In group A, 2 were genotype B, 6 were genotype C; In group B, 6 were genotype B, 3 were genotype C. No significant difference in distribution of serotypes was found between the two groups, either （P = 0.218）. In group A, 2 were adw, 5 were adr, 1 was ayr; In group B, 6 were adw, 3 were adr. The mutation rate of Pre-S1 region at both the DNA level （2.29% vs 1.80%, t = 2.66, P 〉 0.05） and the amino acid level （2.66% vs 1.59%, t = 1.39, P 〉 0.05） was not significantly different between these two groups; ,the mutation rate of Pre-S2 region in group A patients was significantly higher than that in group B at the DNA level （1.74% vs 0.91%, t = 4.68, P 〈 0.01）, but not higher at the amino acid level （3.18% vs 2.05%, t = 1.85, P 〉 0.05）, the mutation rate of S region in group A patients was significantly higher than that in group B at both the DNA level （2.13% vs 0.81%, t = 6.00, P 〈 0.01） and the amino acid level （4.37% vs 1.52%, t = 5.32, P 〈 0.01）. Amino acid substitutions were found both within and beyond the MHR region. The rate of ＂a＂ determinant mutations in these two groups was also found to be signicantly different （P 〈 0.05）. Conclusion Higher HBV S gene mutation rate exists in HBsAg/HBsAb double positive pateints than that in HBsAg （＋）/HBsAb （-） patients.