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

ZOU Chen; MA Yanlu; GAO Yueqiu; ZHANG Xin

doi:10.16305/j.1007-1334.2024.2308107

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

更新时间：2024-07-04

- Association between interleukin‑15 gene polymorphisms and efficacy of integrated traditional Chinese and Western medicine treatment in patients with HBeAg‑negative chronic hepatitis B
- Shanghai Journal of Traditional Chinese Medicine Vol. 58, Issue 7, Pages: 24-30(2024)
- 作者机构：
  
  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）
- 作者简介：
- 基金信息：
- DOI：10.16305/j.1007-1334.2024.2308107
  CLC：
- Published：10 July 2024，
  
  Received：31 August 2023，
- 稿件说明：
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邹晨,马言璐,高月求,等.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[J].上海中医药杂志,2024,58(7):24-30.

ZOU Chen,MA Yanlu,GAO Yueqiu,et al.Association between interleukin‑15 gene polymorphisms and efficacy of integrated traditional Chinese and Western medicine treatment in patients with HBeAg‑negative chronic hepatitis B[J].Shanghai Journal of Traditional Chinese Medicine,2024,58(7):24-30.
邹晨,马言璐,高月求,等.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[J].上海中医药杂志,2024,58(7):24-30. DOI： 10.16305/j.1007-1334.2024.2308107.

ZOU Chen,MA Yanlu,GAO Yueqiu,et al.Association between interleukin‑15 gene polymorphisms and efficacy of integrated traditional Chinese and Western medicine treatment in patients with HBeAg‑negative chronic hepatitis B[J].Shanghai Journal of Traditional Chinese Medicine,2024,58(7):24-30. DOI： 10.16305/j.1007-1334.2024.2308107.

摘要

目的

分析白介素-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

基因的标签单核苷酸多态性（SNPs），并进行基因分型，分析

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（

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（

0.05），对照组血清HBsAg水平降低（

0.05）；组间治疗后比较，血清HBsAg、IL-15水平差异有统计学意义（

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（

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（

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（

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（

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（

0.05）。

结论

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。

Abstract

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 （

=156） and the control group （

=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.

Results

①A 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 （

0.05）. ③Intra-group comparisons before and after treatment showed that serum HBsAg levels decreased and IL-15 levels increased in the treatment group （

0.05）， and serum HBsAg levels decreased in the control group （

0.05）. Inter-group comparisons after treatment showed statistically significant differences in serum HBsAg and IL-15 levels （

0.05）. ④After treatme

nt， serum IL-15 levels increased in patients with a treatment response and decreased in patients without a response in both groups （

0.05）， and patients with a treatment response had higher IL-15 levels than patients without a treatment response in the treatment group （

0.05）. ⑤The results of association analysis revealed significant associations between treatment response and five SNPs： rs6819823， rs2857261， rs10519612， rs10519613， and rs1057972 （

0.05）. ⑥Before treatment， patients in the treatment group with the rs6819823 TT genotype had lower serum IL-15 levels than those with the GG genotype， those with the rs2857261 AA genotype had lower IL-15 levels than those with the GG genotype， and those with the rs1057972 AA genotype had lower IL-15 levels than those with the TT genotype （

0.05）. After treatment， patients carrying the minor alleles of rs6819823， rs2857261， rs10519612， rs10519613， and rs1057972 as homozygotes or heterozygotes showed an increase in serum IL-15 levels （

0.05）.

Conclusion

Genetic variations in the IL-15 gene and changes in IL-15 expression levels are associated with the clinical efficacy of integrated traditional Chinese and Western medicine treatment in patients with HBeAg-negative CHB.

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

Keywords

chronic hepatitis Binterleukin-15single nucleotide polymorphismimmune responseBushen Jianpi Lishi Formulaintegrated traditional Chinese and Western medicine therapy

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