白介素⁃15基因多态性与中西医结合治疗HBeAg阴性慢性乙型肝炎患者疗效的关联性分析  

Association between interleukin⁃15 gene polymorphisms and efficacy of integrated traditional Chinese and Western medicine treatment in patients with HBeAg⁃negative chronic hepatitis B

作　　者：邹晨 马言璐 高月求[1,2] 张鑫[1,2] ZOU Chen;MA Yanlu;GAO Yueqiu;ZHANG Xin(Laboratory of Cellular Immunology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai Key Laboratory of Traditional Chinese Clinical Research,Shanghai 201203,China;Department of Liver Disease,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院细胞免疫实验室,上海市中医临床重点实验室,上海201203 [2]上海中医药大学附属曙光医院肝病科,上海201203

出　　处：《上海中医药杂志》2024年第7期24-30,共7页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81973773);国家“艾滋病和病毒性肝炎等重大传染病防治”科技重大专项(2018ZX10725504);上海中医药大学“杏林百人”人才项目;上海市卫健委上海市临床重点专科(中医专业)建设项目(shslczdzk01201);上海市卫健委上海市进一步加快中医药传承创新发展三年行动计划[ZY(2021-2023)-0103]。

摘　　要：目的分析白介素-15(IL-15)基因多态性与中西医结合治疗乙型肝炎病毒e抗原(HBeAg)阴性慢性乙型肝炎(CHB)患者疗效的关联性。方法将312例HBeAg阴性CHB患者随机分为治疗组、对照组,每组156例,两组均给予西医抗病毒治疗,在此基础上,治疗组加用补肾健脾利湿颗粒,对照组加用补肾健脾利湿颗粒安慰剂,疗程为1年。比较两组的治疗应答率,观察血清IL-15水平的变化情况;挑选IL-15基因的标签单核苷酸多态性(SNPs),并进行基因分型,分析IL-15基因多态性与治疗应答的关联性。结果①最终完成试验者306例,其中治疗组155例、对照组151例。②两组治疗应答率比较,差异无统计学意义(P>0.05)。③治疗前后组内比较,治疗组血清HBsAg水平降低、IL-15水平升高(P<0.05),对照组血清HBsAg水平降低(P<0.05);组间治疗后比较,血清HBsAg、IL-15水平差异有统计学意义(P<0.05)。④治疗后,两组治疗应答患者血清IL-15水平升高、无应答患者血清IL-15水平降低(P<0.05),治疗组应答患者血清IL-15水平高于治疗组无应答患者(P<0.05)。⑤关联分析结果显示,有5个SNPs与治疗应答有显著性关联证据,分别为rs6819823、rs2857261、rs10519612、rs10519613、rs1057972(P<0.05)。⑥治疗前,治疗组应答患者rs6819823 TT基因型血清IL-15水平低于GG基因型、rs2857261 AA基因型血清IL-15水平低于GG基因型、rs1057972 AA基因型患者血清IL-15水平低于TT基因型(P<0.05);治疗后,携带rs6819823、rs2857261、rs10519612、rs10519613、rs1057972最小等位基因的纯合子和杂合子患者血清中IL-15水平上升(P<0.05)。结论IL-15基因遗传变异及IL-15表达水平变化与中西医结合治疗HBeAg阴性CHB的临床疗效存在关联。Objective To analyze the association between interleukin-15(IL-15)gene polymorphisms and the efficacy of integrated traditional Chinese and Western medicine treatment in patients with hepatitis B virus e antigen(HBeAg)-negative chronic hepatitis B(CHB).Methods A total of 312 HBeAg-negative CHB patients were randomly divided into the treatment group(n=156)and the control group(n=156).Both groups received antiviral treatment of Western medicine.In addition,the treatment group received Bushen Jianpi Lishi Granules(Kidney-tonifying and Spleen-Strengthening Dampness-Dispersing Granules),while the control group received a placebo of the granules.Patients in both groups were treated for one year.The treatment response rates of the two groups were compared,and changes in serum IL-15 levels were observed.Tagged single nucleotide polymorphisms(SNPs)of the IL-15 gene were selected for genotyping,and the association between IL-15 gene polymorphisms and treatment response was analyzed.Results①A total of 306 patients completed the trial,including 155 patients in the treatment group and 151 patients in the control group.②There was no statistically significant difference in the treatment response rate between the two groups(P>0.05).③Intra-group comparisons before and after treatment showed that serum HBsAg levels decreased and IL-15 levels increased in the treatment group(P<0.05),and serum HBsAg levels decreased in the control group(P<0.05).Inter-group comparisons after treatment showed statistically significant differences in serum HBsAg and IL-15 levels(P<0.05).④After treatment,serum IL-15 levels increased in patients with a treatment response and decreased in patients without a response in both groups(P<0.05),and patients with a treatment response had higher IL-15 levels than patients without a treatment response in the treatment group(P<0.05).⑤The results of association analysis revealed significant associations between treatment response and five SNPs:rs6819823,rs2857261,rs10519612,rs10519613,and rs1057972(P<0.05)

关 键 词：慢性乙型肝炎 白介素-15 单核苷酸多态性 免疫应答 补肾健脾利湿方 中西医结合疗法 

分 类 号：R512.62[医药卫生—内科学]