在使用硫嘌呤药物的智利患者中,NUDT15中的c.415C>T多态性比TPMT中的多态性更常见。

IF 1.7 3区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pharmacogenetics and genomics Pub Date : 2023-09-01 Epub Date: 2023-08-02 DOI:10.1097/FPC.0000000000000503
Christian von Muhlenbrock, Camila Estay, Natalia Covarrubias, Julio Miranda, Mauricio Venegas
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引用次数: 1

摘要

硫唑嘌呤(AZA)和6-巯基嘌呤(6-MP)是广泛用于治疗自身免疫性疾病的药物。参与AZA和6-MP代谢的酶包括硫嘌呤甲基转移酶(TPMT)和nudix水解酶15(NUDT15)。编码这些酶的基因中单核苷酸多态性的存在可能降低酶活性并导致严重的骨髓抑制。最相关的多态性是NUDT15*3(rs116855232),其中415位的胞嘧啶取代胸腺嘧啶,这反过来导致酶活性的丧失。在之前的一项研究中,发现TPMT基因的多态性加在一起达到3.81%的等位基因频率。没有关于NUDT15基因rs116855232多态性的信息,因此这符合本报告的目的。对智利成年患者的血液样本进行回顾性分析,这些患者具有使用AZA或6-MP治疗不同病理的适应症,并接受了TPMT基因多态性研究。共分析了253份血液样本。在253例患者中,47例出现NUDT15基因c.415C>T多态性,3例为纯合子,44例为杂合子。四名NUDT15杂合患者的TPMT基因也有*3A变体,也是杂合的。发现的次要T等位基因的等位基因频率(9.88%)与亚裔患者的等位频率非常相似,远高于欧洲高加索或拉丁美洲人群的报告频率。
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The c.415C>T polymorphism in NUDT15 is more frequent than the polymorphisms in TPMT in Chilean patients who use thiopurine drugs.

Azathioprine (AZA) and 6-mercaptopurine (6-MP) are drugs widely used in the treatment of autoimmune diseases. Among the enzymes involved in the metabolism of AZA and 6-MP are thiopurine methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15). The existence of single nucleotide polymorphisms in the genes that code for these enzymes could decreased enzymatic activity AND lead to severe myelosuppression. The most relevant polymorphism is NUDT15*3 (rs116855232), where the replacement of cytosine for thymine at position 415, which in turn leads to a loss of enzymatic activity. In a previous study, it was identified that together the polymorphisms in the TPMT gene reach an allelic frequency of 3.81%. There is no information regarding the rs116855232 polymorphism in the NUDT15 gene, so this corresponds to the objective of this report. Blood samples from Chilean adult patients with indications for the use of AZA or 6-MP for different pathologies and who had undergone a TPMT gene polymorphism study were retrospectively analyzed. A total of 253 blood samples were analyzed. Of the 253 patients, 47 presented the c.415C>T polymorphism in the NUDT15 gene, 3 being homozygous and 44 heterozygous. Four of the heterozygous patients for NUDT15 also had the *3A variant in the TPMT gene, also heterozygous. The allelic frequency of the minor T allele found (9.88%) was very similar to that found in patients of Asian origin, and much higher than that reported for the European Caucasian or Latin American population.

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来源期刊
Pharmacogenetics and genomics
Pharmacogenetics and genomics 医学-生物工程与应用微生物
CiteScore
3.20
自引率
3.80%
发文量
47
审稿时长
3 months
期刊介绍: ​​​​Pharmacogenetics and Genomics is devoted to the rapid publication of research papers, brief review articles and short communications on genetic determinants in response to drugs and other chemicals in humans and animals. The Journal brings together papers from the entire spectrum of biomedical research and science, including biochemistry, bioinformatics, clinical pharmacology, clinical pharmacy, epidemiology, genetics, genomics, molecular biology, pharmacology, pharmaceutical sciences, and toxicology. Under a single cover, the Journal provides a forum for all aspects of the genetics and genomics of host response to exogenous chemicals: from the gene to the clinic.
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