CTLA-4基因多态性与乙肝相关性肝硬化患者肝移植术后复发的关联性分析

The correlation between CTLA-4 gene polymorphism and the recurrence in patients with hepatitis B associated liver cirrhosis after liver transplantation

目的分析细胞毒性T淋巴细胞相关抗原4(CTLA-4)基因多态性与乙肝相关性肝硬化患者肝移植术后复发的关系。方法收集2007年1月至2014年2月于湖北医药学院附属人民医院接受肝移植术治疗的乙肝相关性肝硬化46例患者的临床资料,所有患者术后均随访2年,按是否分复发分为复发组和未复发组,均留取肝组织样本,采用聚合酶链反应(PCR)扩增CTLA-4基因,应用PCR-限制性片段长度多态性聚合酶链反应(PCR-RFLP)技术测序,检测受体CTLA-4基因多态性,分析CTLA-4基因多态性与肝移植术后乙肝复发的关系。结果本组肝移植术9例复发,复发率为19. 57%,复发时间(8. 41±1. 6)个月;复发患者术前HBV DNA浓度及术后HBs Ab滴度均低于未复发患者(P <0. 05),其CTLA-4+49位点携带AA型基因频率及CTLA-4启动子1661A/G位点携带AG+GG基因型频率高于未复发患者(P <0. 05);术后HBs Ab滴度(OR=2. 178)、携带GA基因型(OR=3. 041)、携带AG+GG基因型(OR=2. 126)均与乙肝相关性肝硬化肝移植术后复发有关。结论术后HBs Ab滴度改变、CTLA-4+49位点及1661位点基因多态性均可导致乙肝相关性肝硬化肝移植术后复发。

Objective To analyze the relationship between the cytotoxic T lymphocyte associated antigen 4 （CTLA-4） gene polymorphism and the recurrence in patients with hepatitis B associated liver cirrhosis after liver transplantation Methods The clinical data of 46 patients with hepatitis B associated liver cirrhosis treated by liver transplantation in the Affiliated People＇ s Hospital of Hubei Medical College from Jan. 2007 to Feb. 2014 were collected. All patients were followed-up for 2 years alter operation. According to the presence of recurrence, the patients were divided into regroup and non-recurrence group. Liver tissue samples were collected. The CTLA-4 gene was amplified by poly- hain reaction （PCR）, and the PCR-restriction fragment length polymorphism （PCR-RFLP） was used for sequencing.The polymorphism of receptor CTLA-4 gene was detected and the relationship between CTLA-4 gene polymorphism and recurrence of hepatitis B alter liver transplantation was analyzed. Results There were 9 cases with recurrence alter liver transplantation in the study. The recurrence rate was 19.57% , and the recurrence time was （8.41 ± 1.6） months. The preoperative concentration of HBV-DNA and postoperative HBsAb titers in recurrence group were lower than those in non-recurrence group （P 〈 0.05）. The proportions of CTLA-4 ＋ 49 locus canting AA type gene frequency and CTLA-4 promoter 1661 A/G locus canting AG ＋ GG genotype frequencies were higher than those in non-recurrence group （P 〈 0.05 ）. Postoperative HBsAb titer （ OR = 2. 178 ）, carrying GA genotype （ OR = 3. 041 ） and carrying AG ＋ GG genotype （OR = 2. 126） were related to the recurrence of hepatitis B associated liver cirrhosis alter liver transplantation. Conclusion The change of HBsAb titer, the CTLA-4 ＋ 49 locus and the 1661 locus gene polymorphism can lead to the recurrence of hepatitis B associated liver cirrhosis alter liver transplantation.