Work

Association of genetic variants in TPMT, ITPA, and NUDT15 with azathioprine-induced myelosuppression in southwest china patients with autoimmune hepatitis

Year: 2021

Type: article

Abstract: Aims: To investigate the influence of TPMT*3C, ITPA, NUDT15, and 6-thioguanine nucleotides (6-TGN) on AZA-induced myelosuppression in Southwest China AIH patients. Methods: A total of 113 Chinese AIH patients with AZA maintenance treatment were evaluated. Collect the relevant clinical data of patients from the hospital information system. TPMT*3C(rs1142345), ITPA(rs1127354) and NUDT15(rs116855232) genotyping was detected by TaqMan double fluorescent probe. The concentration of 6-TGN was determined using UPLC-MS/MS method. Results: 40 (35.4%) patients had different degrees of myelosuppression. The NUDT15 variant was associated with leukopenia (P=8.26X10-7; OR=7.5; 95% CI, 3.08–18.3) and neutropenia (P=3.54X10-6; OR=8.05; 95% CI, 2.96–21.9). However, no significant association was observed for TPMT*3C and ITPA variants (P>0.05). There was no significant difference of 6-TGN concentration between patients with or without myelosuppression (P= 0.556), and no association was found in patients with TPMT*3C, ITPA, NUDT15 variants alleles (P>0.05). However, we found that the body mass index may affect the corrected 6-TGN level (P=0.026). Conclusion: Our study once again confirmed that NUDT15 variants are a potential independent risk predictor for AZA-induced leukopenia and neutropenia. Also, we found that the detection of 6-TGN concentration in red blood cells does not reflect AZA treatment's efficacy and toxicity. New biomarkers for AZA therapeutic drug monitoring need further research to explore.

Source: Scientific Reports

DOI: 10.1038/s41598-021-87095-0