Fan Xiaoli, Yin Dandan, Men Ruoting, Xu Heng, Yang Li
Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China.
Department of Laboratory Medicine, National Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy and Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China.
Front Pharmacol. 2019 Apr 9;10:346. doi: 10.3389/fphar.2019.00346. eCollection 2019.
The aim of this study was to investigate the influence of and thiopurine S-methyltransferase () on azathioprine (AZA) induced leukopenia in patients with autoimmune hepatitis (AIH) and related cirrhosis. A total of 149 Chinese AIH patients with a history of AZA treatment were retrospectively evaluated. The clinical and epidemiological characteristics of the patients were obtained from an electronic database and reviewed. (rs116855232) and (rs1142345) SNPs were genotyped using a PCR method. Twelve patients developed leukopenia, and this adverse drug reaction was significantly associated with the T risk allele in [ < 0.00001, odds ratio = 20.41; 95% confidence interval (CI) (7.84, 53.13)], with the sensitivity and specificity of 91.67 and 89.05%, respectively. The median maintenance dosages for patients with the rs116855232 CC and CT genotypes were 1.23 (0.95, 1.53) mg ⋅ kg ⋅ d and 0.96 (0.83, 1.19) mg ⋅ kg ⋅ d, respectively ( = 0.028). In contrast, no significant association was observed for genotypes. Notably, subgroup analysis of the 13 patients with leukopenia before therapy, these white blood cell (WBC) counts did not show further reduction after AZA treatment and maintenance dosage was 1.13 (0.94, 1.60) mg ⋅ kg ⋅ d. Therefore, polymorphism is significantly associated with thiopurine-induced leukopenia in Chinese patients with AIH and related cirrhosis. Adjusting the AZA dosage should be considered in patients according to the genotypes.
本研究旨在探讨[此处原文缺失具体基因名称]和硫嘌呤S-甲基转移酶（TPMT）对自身免疫性肝炎（AIH）及相关肝硬化患者中硫唑嘌呤（AZA）所致白细胞减少的影响。对149例有AZA治疗史的中国AIH患者进行了回顾性评估。从电子数据库中获取并审查了患者的临床和流行病学特征。采用聚合酶链反应（PCR）方法对[此处原文缺失具体基因名称]（rs116855232）和TPMT（rs1142345）单核苷酸多态性（SNP）进行基因分型。12例患者出现白细胞减少，这种药物不良反应与[此处原文缺失具体基因名称]中的T风险等位基因显著相关[P < 0.00001，比值比 = 20.41；95%置信区间（CI）（7.84，53.13）]，敏感性和特异性分别为91.67%和89.05%。rs116855232基因CC和CT基因型患者的维持剂量中位数分别为1.23（0.95，1.53）mg·kg·d和0.96（0.83，1.19）mg·kg·d（P = 0.028）。相比之下，未观察到TPMT基因型有显著关联。值得注意的是，对13例治疗前白细胞减少的患者进行亚组分析，这些患者的白细胞（WBC）计数在AZA治疗后未进一步降低，维持剂量为1.13（0.94，1.60）mg·kg·d。因此，[此处原文缺失具体基因名称]多态性与中国AIH及相关肝硬化患者硫嘌呤诱导的白细胞减少显著相关。应根据[此处原文缺失具体基因名称]基因型考虑对患者调整AZA剂量。
