PTPN2 and Leukopenia in Individuals With Normal TPMT and NUDT15 Metabolizer Status Taking Azathioprine.

ABSTRACT: Leukopenia is a common dose-dependent side effect of azathioprine, often leading to drug discontinuation. Variants in TPMT and NUDT15 are associated with azathioprine-induced leukopenia but only explain 25% of cases. Thus, we aimed to identify novel genetic risk factors among TPMT and NUDT15 normal metabolizers through a genome-wide association study (GWAS). Using BioVU, Vanderbilt's electronic health record linked to genetic data, we assembled a discovery cohort of new users of azathioprine. The analysis was conducted in 1184 new users of azathioprine who had no history of prior thiopurine use or an organ transplant. A replication cohort of 521 patients was derived from All of Us, an NIH-funded project that links healthcare data and genetics. The GWAS was adjusted for sex, age, indication

SUBMITTER: Daniel LL 

PROVIDER: S-EPMC12122386 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature