Thiopurine S-Methyltransferase Polymorphisms Predict Hepatotoxicity in Azathioprine-Treated Patients with Autoimmune Diseases.

Autor: Sheu HS; Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan., Chen YM; Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan.; Department of Medical Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan.; School of Medicine, National Yang-Ming Chiao Tung University, Taipei 30010, Taiwan.; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 40227, Taiwan.; Rong Hsing Research Center for Translational Medicine & Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 40227, Taiwan.; Department of Pharmacy, Taichung Veterans General Hospital, Taichung 40705, Taiwan., Liao YJ; Department of Pharmacy, Taichung Veterans General Hospital, Taichung 40705, Taiwan., Wei CY; Department of Medical Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan., Chen JP; Department of Medical Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan., Lin HJ; Department of Medical Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan., Hung WT; Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan.; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 40227, Taiwan.; Department of Medical Education, Taichung Veterans General Hospital, Taichung 40705, Taiwan., Huang WN; Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan.; School of Medicine, National Yang-Ming Chiao Tung University, Taipei 30010, Taiwan.; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 40227, Taiwan.; College of Business and Management, Ling Tung University, Taichung 408284, Taiwan., Chen YH; Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan.; School of Medicine, National Yang-Ming Chiao Tung University, Taipei 30010, Taiwan.
Jazyk: angličtina
Zdroj: Journal of personalized medicine [J Pers Med] 2022 Aug 28; Vol. 12 (9). Date of Electronic Publication: 2022 Aug 28.
DOI: 10.3390/jpm12091399
Abstrakt: Thiopurine methyltransferase (TPMT) is the rate-limiting enzyme in Azathioprine (AZA) metabolization. Although studies have discussed the association between the TPMT polymorphisms and myelosuppression, the data about the relationship between TPMT genotypes and hepatoxicity in Asian patients remain limited. This study investigated the correlation between TPMT polymorphisms and AZA-related hepatotoxicity. This study enrolled the patients who had prior exposure to AZA from the Taichung Veterans General Hospital (TCVGH)-Taiwan Precision Medicine Initiative (TPMI) cohort. Genetic variants were determined using a single nucleotide polymorphism (SNP) array. Participants were accordingly categorized into normal metabolizer (NM) and non-normal metabolizer (non-NM) groups. From the TCVGH-TPMI cohort, we included 50 TPMT non-NM patients, including 1 poor metabolizer (PM), 49 intermediate metabolizers (IMs), and 1000 NM patients. The non-NM genotype was associated with hepatotoxicity compared with the NM genotype (hazard ratio (HR): 3.85, 95% confidence interval (CI): 1.83−8.10). In the non-NM group, the 3-year cumulative incidence of hepatotoxicity was higher than that in the NM group at 8.5% in the first year and 18.6% in the second and third years (p < 0.001). A TPMT non-NM genotype was associated with the occurrence of hepatotoxicity following AZA therapy. Preemptive testing helps individualize AZA therapy by minimizing the risk of hepatotoxicity.
Databáze: MEDLINE
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