乙型肝炎病毒家族聚集性感染者基因型分布及基础核心启动子和C区变异的研究

Distribution of HBV genotypes and mutations in basic core gene promoter,pre C/C region in infected family clustering members

目的探讨家族聚集性乙肝感染者HBV基因型和基础核心启动子(BCP)、前C/C区变异的特征及其临床意义。方法选择家族聚集性慢性乙型肝炎(CHB)患者98例(来自38个家族)作为研究组,非家族聚集性CHB患者110例作为对照组;应用型特异性引物巢式PCR法检测HBV感染者的HBV基因型,PCR测定BCP、前C/C区核苷酸序列,并且检测患者血清丙氨酸转氨酶(ALT)、总胆红素(TBIL)、白蛋白(ALB)、乙肝五项和HBV-DNA载量等临床指标。结果家族性乙肝母亲和(或)父亲与子女感染组以C基因型为主(52.9%,36/68),家族水平成员感染组和对照组以B基因型为主[分别为73.3%(22/30)、67.3%(74/110)],仅检测到少数B/C和B/D混合型,并且乙肝家族中母亲和(或)父亲与子女感染组C基因型所占百分比高于家族水平成员感染组及对照组(P<0.01)。家族内HBV聚集感染的基因型基本相同,不一致者为混合型。HBV C基因型的家族CHB患者比对照组具有更高的HBV-DNA载量(P<0.01),更高的BCP区A1762T/G1764A双突变率[61.9%(26/42)vs 35.7(10/28),P<0.05]。结论家族聚集性CHB患者HBV基因型可能与传播途径有关,C基因型更易发生垂直传播。HBV C基因型感染并且BCP区A1762T/G1764A双突变可能是家族聚集感染者病情进展的危险因素。

Objective To investigate the distribution of HBV genotypes and the mutations in basic core gene promoter（BCP）,pre C/C region in clustering family patients infected with chronic hepatitis B（CHB）,and to discuss the related clinical significance.Methods A total of 98 CHB patients from 38 family with family clustering features were included in the experimental group,and 110 CHB patients without family clustering features were taken as controls.HBV genotypes were detected in CHB patients by nested PCR with genotype-specific primers.The mutations in BCP and pre C/C region were detected using PCR.Serum ALT,TBIL,ALB,HBV-DNA levels,and hepatitis B antigen and antibody were all examined.Results HBV genotype C was the predominant genotype（52.9%,36/68） in group of parents and their children,and genotype B was the predominant genotype in group of other infected family members（73.3%,22/30） and control group（67.3%,74/110）;the frequency of HBV genotype C in group of parents and their children was significantly higher than other infected family members and control group（P〈0.01）.There were only a few B＋C and B＋D mixed types.On the whole,HBV genotypes from the same family were basically the same.The frequency of BCP A1762T/G1764A mutations in clustering family CHB patients with genotype C（61.9%,26/42） was significantly higher than that in CHB patients with genotype C without family clustering features（35.7%,10/28）（P〈0.05）,so was the HBV-DNA level（P〈0.01）.Conclusion HBV genotype in clustering family is probably associated with the transmission route of virus.HBV genotype C may be easier to transmit from parents to their children.Genotype C and BCP A1762T/G1764A mutations may be associated with the development of CHB in clustering family.