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

Authors :
Heh-Shiang Sheu
Yi-Ming Chen
Yi-Ju Liao
Chia-Yi Wei
Jun-Peng Chen
Hsueh-Ju Lin
Wei-Ting Hung
Wen-Nan Huang
Yi-Hsing Chen
Source :
Journal of Personalized Medicine, Vol 12, Iss 9, p 1399 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

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.

Details

Language :
English
ISSN :
20754426
Volume :
12
Issue :
9
Database :
Directory of Open Access Journals
Journal :
Journal of Personalized Medicine
Publication Type :
Academic Journal
Accession number :
edsdoj.034f1f00b4600bb3dd22dd17ae78b
Document Type :
article
Full Text :
https://doi.org/10.3390/jpm12091399