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药物性肝损伤伴自身免疫现象患者血清γ干扰素诱导蛋白10水平及其单核苷酸多态性
Serum interferon-gamma-induced protein-10 level and gene polymorphism in patients with drug-induced liver injury accompanied by autoimmune phenomena
文章发布日期:2020年02月17日  来源:  作者:任姗,杜晓菲,黄云丽,等  点击次数:220次  下载次数:63次

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【摘要】:目的 探讨药物性肝损伤伴自身免疫现象(AI-DILI)患者血清γ干扰素诱导蛋白10(IP-10)单核苷酸基因多态性(SNP)及其表达水平。方法 选取2016年10月-2019年6月首都医科大学附属北京佑安医院肝病免疫科诊治的药物性肝损伤(DILI)患者168例,分为AI-DILI组(n=72)与非AI-DILI组(n=96),检测IP-10 rs56061981位点SNP及血清IP-10水平。比较两组间IP-10水平及SNP的差异性,并与AI-DILI的发生进行分析。等位基因频率直接由基因分型结果计算,采用χ2检验进行Hardy-Weinberg平衡分析。计量资料2组间比较采用t检验和Mann-Whitney U检验,不同时间点比较采用重复测量资料方差分析;计数资料采用χ2检验或Fisher’s确切概率法。相关性分析采用pearson法。采用受试者工作特征曲线(ROC曲线)分析基线IP-10水平对AI-DILI的预测作用。结果 AI-DILI组自身抗体阳性率为91.67%,非AI-DILI组自身抗体阳性率为12.5%,差异有统计学意义(χ2 =103.8,P<0.05)。AI-DILI组CC基因型频率显著高于非AI-DILI组(77.78% vs 62.50%,χ2=4.592,P=0.03),同时AI-DILI组携带C等位基因频率显著高于非AI-DILI组(86.11% vs 72.92%,χ2=4.41,P=0.04)。AI-DILI患者基线IP-10水平显著高于非AI-DILI患者[(627.99±198.07) pg/ml vs (378.13±218.45) pg/ml,t=7.34, P<0.05),与基线AST水平及AIH评分呈正相关(r值分别为0.67、0.79,P值均<0.05)。基线IP-10预测AI-DILI的ROC曲线下面积为0.832,敏感度、特异度分别为0.846、0.867,最佳阈值为527.03 pg/ml。CC基因型联合基线IP-10≥527.03 pg/ml预测AI-DILI发生,其阳性预测值为92.84%,阴性预测值为8.33%。结论 IP-10 rs 56061981 CC基因型与AI-DILI的发生有关,并影响AI-DILI血清IP-10表达,二者联合预测AI-DILI效能显著提高。
【Abstract】:Objective To investigate the single nucleotide polymorphism (SNP) and serum expression of interferon-gamma-induced protein 10 (IP-10) in patients with drug-induced liver injury accompanied by autoimmune phenomena (AI-DILI). Methods A total of 168 patients with drug-induced liver injury (DILI) who were diagnosed and treated in Beijing YouAn Hospital, Capital Medical University, from October 2016 to June 2019 were enrolled and divided into AI-DILI group(n=72) and non-AI-DILI group(n=96). The SNP of IP-10 rs56061981 locus was detected and the serum level of IP-10 was measured. The two groups were compared in terms of IP-10 level and SNP genotype, and their association with the development of AI-DILI was analyzed. Allele frequency was calculated based on genotype results, and the chi-square test was used for Hardy-Weinberg equilibrium analysis. The t-test and the Mann-Whitney U test were used for comparison between two groups; a repeated measures analysis of variance was used for comparison between different time points; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The Pearson correlation analysis was used to investigate correlation. The receiver operating characteristic (ROC) curve was used to analyze the value of baseline IP-10 level in predicting AI-DILI. Results There was a significant difference in the positive rate of autoantibody between the AI-DILI group and the non-AI-DILI group (91.67% vs 12.5%, χ2= 103.8, P<0.05). Compared with the non-AI-DILI group, the AI-DILI group had significantly higher distribution frequency of CC genotype (77.78% vs 62.50%, χ2=4.592, P=0.03) and frequency of C allele (86.11% vs 72.92%, χ2=4.41, P=0.04). The AI-DILI group had a significantly higher baseline IL-10 level than the non-AI-DILI group (627.99±198.07 pg/ml vs 378.13±218.45 pg/ml, t=7.34, P<0.05), and baseline IL-10 level was positively correlated with baseline aspartate aminotransferase level and AIH score (r=0.67 and 0.79, both P<0.05). At the optimal cut-off value of 527.03 pg/ml, baseline IP-10 level had a sensitivity of 0.846, a specificity of 0.867, and an area under the ROC curve of 0.832 in predicting AI-DILI. CC genotype combined with a baseline IP-10 level of ≥527.03 pg/ml had a positive predictive value of 92.84% and a negative predictive value of 86.33% in predicting the development of AI-DILI. Conclusion CC genotype of IP-10 rs56061981 is associated with the development of AI-DILI and affects the serum expression of IP-10, and the combination of CC genotype and IP-10 expression has a high value in predicting AI-DILI.
【关键字】:药物性肝损伤; 肝炎, 自身免疫; 多态性, 单核苷酸; γ干扰素诱导蛋白-10
【Key words】:drug-induced liver injury; hepatitis, autoimmunity; polymorphism, single nucleotide; interferon-gamma-induced protein-10
【引证本文】:REN S, DU XF, HUANG YL, et al. Serum interferon-gamma-induced protein-10 level and gene polymorphism in patients with drug-induced liver injury accompanied by autoimmune phenomena[J]. J Clin Hepatol, 2020, 36(3): 602-607. (in Chinese)
任姗, 杜晓菲, 黄云丽, 等. 药物性肝损伤伴自身免疫现象患者血清γ干扰素诱导蛋白10水平及其单核苷酸多态性[J]. 临床肝胆病杂志, 2020, 36(3): 602-607.

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