NUDT15 R139C Variants Increase the Risk of Azathioprine-Induced Leukopenia in Chinese Autoimmune Patients

Abstract

The aim of this study was to investigate the influence of <i>NUDT15 R139C</i>, thiopurine S-methyltransferase (<i>TPMT</i>), and 6-TGN on azathioprine (AZA) induced leukopenia in Chinese autoimmune patients. Among 87 enrolled patients, 23 (26.4%) had leukopenia. The <i>NUDT15 R139C</i> variant was associated with leukopenia (<i>p</i> = 1.86 × 10^-7; OR: 7.59; 95% CI: 3.16-18.21). However, <i>TPMT</i> genotype was not shown to be correlated with the incidence of leukopenia (<i>p</i> = 0.95). There was no significant difference of 6-TGN concentration between patients with or without leukopenia (<i>p</i> = 0.15) and no association was found in patients with <i>NUDT15 R139C</i> variants alleles (<i>p</i> = 0.62). Finally, we found that the range of 6-TGN concentrations in autoimmune diseases was much lower than the established 6-TGN monitoring range for inflammatory bowel diseases. Therefore, the variant of <i>NUDT15 R139C</i> is strongly associated with AZA-induced leukopenia in Chinese patients with various autoimmune diseases such as systemic lupus erythematosus, Sjögren's syndrome, etc.