XDH genotypes through gene–gene interactions with NUDT15 affect azathioprine-induced leukopenia in Chinese patients

Abstract

Aim: To investigate whether genotypes of XDH, GMPS and MOCOS were associated with azathioprine-induced adverse drug reaction (ADR) and had the gene–gene interactions with NUDT15 rs116855232 to induce leukopenia. Methods: Patients who had taken azathioprine were recruited. Genotyping of those gene was performed. Risk factor to ADR was analyzed by logistic regression. The generalized multifactor dimensionality reduction (GMDR) was assessed based on gene–gene interactions with ADR. Results: A total of 111 patients were included in this study, all of whom were Han Chinese. XDH rs2295475 was a risk factor of myelotoxicity (p = 0.022). NUDT15 rs116855232 was a risk factor of myelotoxicity, grade ≥2 leukopenia and drug treatment termination (p-values were <0.05). Rs2295475 and rs116855232 had a gene–gene interaction. The model was associated with grade ≥2 leukopenia (OR: 17.99; 95% CI: 4.11–78.81). Conclusion: Combined testing genotype for rs2295475 and rs116855232 could improve the prediction of azathioprine-induced leukopenia.