CXCR5基因多态性与慢性乙型肝炎患者核苷类药物停药后临床复发的关联性  

Association between CXCR5 gene polymorphism and clinical relapse after discontinuation of nucleoside drugs in patients with chronic hepatitis B

作　　者：唐雪峰[1,2,3,4] 张蝶 张磊 卢晋英[1,2,3,4] 张淑文 TANG Xue-feng;ZHANG Die;ZHANG Lei;LU Jin-ying;ZHANG Shu-wen(Tianjin Third Central Hospital,Tianjin 300170,China;不详)

机构地区：[1]天津市第三中心医院检验科,天津300170 [2]天津市重症疾病体外生命支持重点实验室,天津300170 [3]天津市人工细胞工程技术研究中心,天津300170 [4]天津市肝胆研究所,天津300170

出　　处：《中华医院感染学杂志》2022年第4期526-530,共5页Chinese Journal of Nosocomiology

基　　金：天津市自然科学基金(青年项目)资助项目(16JCQNJC11600)。

摘　　要：目的 探讨C-X-C趋化因子受体5(CXCR5)基因多态性与慢性乙型肝炎(CHB)患者核苷类药物停药后临床复发的关系。方法 选择天津市第三中心医院肝内科2017年2-10月进行抗病毒治疗的慢性乙肝患者112例符合停药标准自行停药作为研究对象,根据其核苷(酸)类似物(NAs)方案治疗停药后是否发生临床复发分为复发组(n=36)和未复发组(n=76)。患者在停药后每12周接受一次随访,在复查时接受乙肝表面抗原(HBsAg)、丙氨酸氨基转移酶(ALT)及CXCR5血清水平检测。采用聚合酶链式扩增反应(PCR)对模板DNA中CXCR5基因目标序列进行扩增后,收集反应产物送公司测序,将测序结果进行比对。结果 停药时基线HBsAg、ALT和CXCR5水平比较差异无统计学意义;停药12周、24周、36周和48周时,复发组HBsAg、ALT和CXCR5水平均高于非复发组(P<0.05);复发组CXCR5基因rs676925位点CC基因型、C等位基因频率(61.11%、75.00%)高于未复发组,GG基因型、G等位基因频率(11.11%、25.00%)低于未复发组(P<0.05);校正性别、年龄、NAs治疗前HBeAg状态和NA治疗年限后,血清CXCR5升高、CXCR5基因rs676925位点CC基因型、CXCR5基因rs676925位点C等位基因是NAs治疗CHB患者临床复发的独立危险因素(P<0.05)。结论 血清CXCR5是预测CHB患者NAs治疗停药后临床复发的有价值因素,不同个体间临床复发情况的差异可能与CXCR5基因rs676925位点突变有关。OBJECTIVE To investigate the relationship between C-X-C chemokine receptor 5(CXCR5) gene polymorphism and clinical recurrence of patients with chronic hepatitis B(CHB) after discontinuation of nucleoside drugs. METHODS Totally 102 patients with chronic hepatitis B who met the discontinuation criteria and discontinued treatment by themselves, treated with antiviral therapy from Feb. 2017 to Oct. 2017 in the Department of Hepatology of Tianjin Third Central Hospital were selected as the research subjects. According to their NA regimen whether the clinical recurrence occurred after the discontinuation of the drug, they were divided into recurrence group(n=36) and non-recurrence group(n=76). The patients received follow-up every 12 weeks after stopping the drug, and serum hepatitis B surface antigen(HBsAg), alanine aminotransferase(ALT) and CXCR5 levels were detected during the re-check. After the target sequence of CXCR5 gene in the template DNA was amplified by polymerase chain amplification reaction(PCR), the reaction products were collected and sent to the company for sequencing, and the sequencing results were compared. RESULTS There was no significant difference in baseline HBsAg, ALT and CXCR5 levels at the time of drug withdrawal;at 12, 24, 36, and 48 weeks of drug withdrawal, the levels of HBsAg, ALT and CXCR5 in the relapsed group were significantly higher than those in the non-relapsed group(P<0.05);The frequency of CC genotype and C alleles(61.11%, 75.00%) of CXCR5 gene at the rs676925 site in the recurrence group was significantly higher than that of the non-recurring group, and the frequencies of GG genotype and G allele( 11.11%, 25.00%) were significantly lower than those of the non-relapsed group(P<0.05). After adjusting for gender, age, HBeAg status before NAs treatment, and NA treatment years, serum CXCR5 increased, CC genotype of CXCR5 gene at rs676925 locus, C allele of CXCR5 gene at rs676925 locus were independent risk factors of clinical recurrence in CHB patients treated with NAs(P<0.05). CONCL

关 键 词：C-X-C趋化因子受体5 慢性乙型肝炎 核苷类药物 临床复发 易感性 

分 类 号：R512.62[医药卫生—内科学]