乙型肝炎病毒基本核心启动子区1762/1764双突变与基因型和HBeAg血清学转换的关系

Relationship between HBV basic core promoter coexistent mutation of 1762/1764 sites and viral genotypes or HBeAg seroconversion

目的:观察慢性乙型肝炎(chronic hepatitis B,CHB)自然史中不同基因型乙型肝炎病毒(HBV)基本核心启动子(basic core promoter,BCP)区1762(A-T)/1764(G-A)双突变的分布,以及与中国常见HBV基因型的关系和对HBeAg血清学转换的影响。方法:随机选取168例未进行过抗病毒治疗的CHB患者,利用制备的特异性TaqMan MGB探针,采用特异性探针实时荧光定量PCR(PSRT-PCR)方法对其血清行B、C基因型分型和双突变定量检测,比较双突变在B、C基因型的分布情况;同时采用微粒子化学发光免疫法(CMIA)检测血清HBeAg和抗HBe,比较B、C基因型各组双突变株和野生株病毒的HBeAg血清学转换。结果:C基因型CHB患者BCP区1762/1764双突变率(70.65%)明显高于B基因型(29.17%,P=0.000)。观察HBeAg阴性CHB患者比例,B基因野生组明显高于其双突变组(28.57%,P=0.004)和C基因野生组(22.22%,P=0.000);C基因双突变组(63.08%)明显高于其野生组(22.22%,P=0.000)和B基因双突变组(28.57%,P=0.018)。在所有HBeAg阴性患者中,B基因野生组抗HBe阳性率(84.00%)高于其双突变组(0.00%,P=0.003)和C基因野生组(16.67%,P=0.004);C基因双突变组抗HBe阳性率(19.51%)与其野生组(16.67%)和B基因双突变组(0.00%)比较,差异无统计学意义(P均=1.000)。结论:在我国慢性HBV感染人群中,C基因型患者更易发生BCP区1762/1764双突变;B基因野生型患者易产生HBeAg阴性并伴有抗HBe阳性,HBeAg血清学转换较彻底;而C基因双突变患者易产生HBeAg阴性但不伴有抗HBe阳性,HBeAg血清学转换不彻底。

Objective:Based on the results of the incidence rates of the basic core promoter(BCP) coexistent mutation of 1762/1764 sites and the expression of hepatitis B virus(HBV) e antigen(HBeAg) and its antibody in chronic hepatitis B(CHB) patients with common viral genotypes in China,to investigate the relationship between the coexistent mutation and both of viral genotypes and HBeAg seroconversion in the natural course of chronic HBV infection.Methods:The sera of 168 CHB patients randomly selected with no previous history of antiviral therapy were detected.Their viral genotypes and coexistent mutation were determined by probe-specific real-time polymerase chain reaction(PSRT-PCR) that applied TaqMan MGB probe which had been designed and made exactly in past time;and HBeAg and its antibody(HBeAb) titer were measured by chemiluminescence microparticle immunoassay(CMIA).Results:The coexistent mutation in BCP 1762/1764sites was significantly more frequent in genotype C HBV patients than that in genotype B patients(70.65% vs29.17%,P = 0.000).The wild genotype B group had a significantly higher proportion of HBeAg-negative HBV patients than the coexistent mutation genotype B group(73.53% vs 28.57%,P = 0.004) and the wild genotype C group(73.53% vs 22.22%,P = 0.000);the coexistent mutation genotype C group had a significantly higher proportion of HBeAg-negative HBV patients than the wild genotype C group(63.08% vs22.22%,P = 0.000) and the coexistent mutation genotype B group(63.08% vs 28.57%,P = 0.018).In all HBeAg-negative patients,the wild genotype B group had a more higher HBeAb-positive rate than the coexistent mutation genotype B group(84.00% vs 0.00%,P = 0.003) and the wild genotype C group(84.00% vs16.67%,P = 0.004),while there was no significant difference between the coexistent mutation genotype C group and the wild genotype C group(19.51% vs 16.67%,P = 1.000) and the coexistent mutation genotype B group(19.51% vs 0.00%,P = 1.000).Conclusions:During the natural course of chronic HBV infection in China,the BCP coexistent mutation of 1764/1762 sites was more common in patients with genotype C,compared with genotype B;and the thorough HBeAg seroconversion occurred more frequently in wild genotype B HBeAg-negative patients,with HBeAb-positive;while the halfway HBeAg seroconversion occured in coexistent mutation genotype C HBeAg-negative patients,without HBeAb-positive.