Introduction: Azathioprine is a synthetic purine analogue derived from 6-mercaptopurine which acts by disrupting nucleic acid synthesis and interfering with T cell activation. It is effective in dermatology diseases related to the immune system. However, its side effects, including severe neutropenia, kept patients from using it. Mutations in thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphohydrolase (ITPA) genes account for the major genetic polymorphism markers for azathioprine adverse risk factors in Caucasians, but not in Asians. The predictive value of the nucleoside diphosphate-linked moiety X motif 15 gene (NUDT15) has been studied in various diseases among different populations. The aim of our study was to determine the contribution of NUDT15 mutations in azathioprine-induced neutropenia in Han Chinese patients with dermatologic diseases.
Methods: The study enrolled all consecutive patients, older than 13 years old, with dermatological diseases currently treated orally with azathioprine in our clinic. Samples were also collected from patients with documented leukopenia in our prior study that examined the association between TPMT, ITPA, and neutropenia after informed reconsent. Complete blood count, differential count, and hepatic and renal function were checked regularly. The DNA samples for NUDT15 genotype were obtained from the patients.
Results: In total, we enrolled 56 patients (39 male, 17 female). The NUDT15 genotypes are mostly C/C (N = 36, 64.29%). Heterozygous variant (C/T) accounts for 30.36% (N = 17) and homozygous variant (T/T) accounts for 5.36% (N = 3). Among these patients, 15 patients (26.79%) developed neutropenia, including all three patients carry homozygous variant (T/T). The age-, sex-, and dose-adjusted risk of heterozygous variant compared to wild type is 9.383 (95% CI 1.32-66.96).
Conclusions: Pretreatment screening of NUDT15 might reduce the chance of azathioprine-induced neutropenia in Han Chinese patients with dermatologic diseases.
Keywords: Adverse drug reactions; Azathioprine; Dermatologic diseases; Han Chinese; Neutropenia; Nucleoside diphosphate-linked moiety X motif 15 (NUDT15); Pretreatment screening.