NUDT15单倍型和双倍型预测炎症性肠病患者硫嘌呤诱导的白细胞减少症以及长期暴露于硫唑嘌呤对血液学指标的影响

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Journal of Clinical Pharmacy and Therapeutics Pub Date : 2023-07-27 DOI:10.1155/2023/3000409

Wenyu Jiang, Shasha Wu, Meijiao Lu, Jiahui Tian, X. Cui, Xiaqiong Mao, C. Jiao, N. Tang, Jingjing Ma, Hongjie Zhang

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The relationship between NUDT15 haplotypes and diplotypes and leukopenia was analyzed. Results. The haplotypes NUDT15 c.415C > T and c.36_37insGGAGTC as well as the diplotypes NUDT15 \n \n \n \n ∗\n \n \n 1/\n \n \n \n ∗\n \n \n 2, \n \n \n \n ∗\n \n \n 3/\n \n \n \n ∗\n \n \n 3, and \n \n \n \n ∗\n \n \n 3/\n \n \n \n ∗\n \n \n 5 were significantly associated with AZA-induced leukopenia. Only one patient with NUDT15 c.52G > A experienced leukopenia. NUDT15 \n \n \n \n ∗\n \n \n 1/\n \n \n \n ∗\n \n \n 3 was not associated with leukopenia. After AZA initiation, the WBC count showed a downward trend in both wild types and mutants. The mean of WBC count in the mutant group at 1st month after AZA initiation was lower than that in the wild-type group (\n \n P\n =\n 0.006\n \n ). The MCV increased gradually in mutant cases (\n \n P\n =\n 0.039\n \n ), and the differences were obvious at 6th and 12th months compared with the baseline (\n \n P\n =\n 0.014\n \n a\n n\n d\n \n P\n =\n 0.042\n \n , respectively). The PLT count showed a decreasing trend in the mutant group, but there was no difference until 11 months after initiating treatment (\n \n P\n =\n 0.023\n \n ). The final dose of AZA in the NUDT15 mutant group was significantly lower than that in the wild-type group (\n \n P\n =\n 0.006\n \n ). Conclusion. NUDT15 polymorphisms may be an appropriate predictor of AZA abnormal hematologic indices in IBD patients. It is necessary for IBD patients to monitor hematological indices and optimize AZA therapy.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":" ","pages":""},"PeriodicalIF":2.1000,"publicationDate":"2023-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"NUDT15 Haplotypes and Diplotypes Predict Thiopurine-Induced Leukopenia and the Influence of Prolonged Exposure to Azathioprine on Hematologic Indices in Patients with Inflammatory Bowel Diseases\",\"authors\":\"Wenyu Jiang, Shasha Wu, Meijiao Lu, Jiahui Tian, X. Cui, Xiaqiong Mao, C. Jiao, N. Tang, Jingjing Ma, Hongjie Zhang\",\"doi\":\"10.1155/2023/3000409\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background. NUDT15 gene polymorphisms have been identified to predispose Asian patients with an inflammatory bowel disease (IBD) to thiopurine-induced leukopenia. 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引用次数: 0

摘要

背景。NUDT15基因多态性已被确定使亚洲炎症性肠病(IBD)患者易患硫嘌呤诱导的白细胞减少症。本研究预测了NUDT15单倍型和双倍型对硫唑嘌呤(AZA)诱导的白细胞减少的影响，以及AZA对IBD血液学参数的长期影响。方法:对194例IBD患者进行NUDT15基因型检测。我们收集了80例接受AZA治疗的患者的临床资料，包括不良事件、剂量、开始AZA治疗后的白细胞(WBC)计数、血小板(PLT)计数和平均红细胞体积(MCV)。无不良事件和停药的患者随访至少1年。分析了NUDT15单倍型和双倍型与白细胞减少症的关系。结果。单倍型NUDT15、c.415C、> T和c.36_37insGGAGTC以及双倍型NUDT15∗1/∗2、∗3/∗3和∗3/∗5与aza诱导的白细胞减少显著相关。只有1例NUDT15 c.52G > A出现白细胞减少。NUDT15∗1/∗3与白细胞减少无关。在AZA启动后，野生型和突变型白细胞计数均呈下降趋势。突变组在AZA启动后第1个月WBC计数平均值低于野生型组(P = 0.006)。突变病例MCV逐渐升高(P = 0.039)，在第6、12个月与基线比较差异明显(P = 0.014、P = 0.042)。突变组PLT计数呈下降趋势，但直到治疗后11个月才有差异(P = 0.023)。NUDT15突变体组AZA的终剂量显著低于野生型组(P = 0.006)。结论。NUDT15多态性可能是IBD患者AZA异常血液学指标的适当预测因子。IBD患者有必要监测血液学指标，优化AZA治疗。

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NUDT15 Haplotypes and Diplotypes Predict Thiopurine-Induced Leukopenia and the Influence of Prolonged Exposure to Azathioprine on Hematologic Indices in Patients with Inflammatory Bowel Diseases

Background. NUDT15 gene polymorphisms have been identified to predispose Asian patients with an inflammatory bowel disease (IBD) to thiopurine-induced leukopenia. This study predicted the influence of NUDT15 haplotypes and diplotypes on azathioprine (AZA)-induced leukopenia as well as the long-term influence of AZA on hematologic parameters in IBD. Methods. 194 IBD patients were tested for NUDT15 genotypes. We collected clinical data of 80 patients with AZA treatment including adverse events, dosage, white blood cell (WBC) count, platelet (PLT) count, and mean corpuscular volume (MCV) after AZA initiation. Patients without adverse events and drug withdrawal were followed up for at least one year. The relationship between NUDT15 haplotypes and diplotypes and leukopenia was analyzed. Results. The haplotypes NUDT15 c.415C > T and c.36_37insGGAGTC as well as the diplotypes NUDT15 ∗ 1/ ∗ 2, ∗ 3/ ∗ 3, and ∗ 3/ ∗ 5 were significantly associated with AZA-induced leukopenia. Only one patient with NUDT15 c.52G > A experienced leukopenia. NUDT15 ∗ 1/ ∗ 3 was not associated with leukopenia. After AZA initiation, the WBC count showed a downward trend in both wild types and mutants. The mean of WBC count in the mutant group at 1st month after AZA initiation was lower than that in the wild-type group ( P = 0.006 ). The MCV increased gradually in mutant cases ( P = 0.039 ), and the differences were obvious at 6th and 12th months compared with the baseline ( P = 0.014 a n d P = 0.042 , respectively). The PLT count showed a decreasing trend in the mutant group, but there was no difference until 11 months after initiating treatment ( P = 0.023 ). The final dose of AZA in the NUDT15 mutant group was significantly lower than that in the wild-type group ( P = 0.006 ). Conclusion. NUDT15 polymorphisms may be an appropriate predictor of AZA abnormal hematologic indices in IBD patients. It is necessary for IBD patients to monitor hematological indices and optimize AZA therapy.

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来源期刊

Journal of Clinical Pharmacy and Therapeutics 医学-药学

CiteScore

4.10

自引率

5.00%

发文量

226

审稿时长

6 months

期刊介绍： The Journal of Clinical Pharmacy and Therapeutics provides a forum for clinicians, pharmacists and pharmacologists to explore and report on issues of common interest. Reports and commentaries on current issues in medical and pharmaceutical practice are encouraged. Papers on evidence-based clinical practice and multidisciplinary collaborative work are particularly welcome. Regular sections in the journal include: editorials, commentaries, reviews (including systematic overviews and meta-analyses), original research and reports, and book reviews. Its scope embraces all aspects of clinical drug development and therapeutics, including: Rational therapeutics Evidence-based practice Safety, cost-effectiveness and clinical efficacy of drugs Drug interactions Clinical impact of drug formulations Pharmacogenetics Personalised, stratified and translational medicine Clinical pharmacokinetics.