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

Aim: To investigate whether genotypes of XDH, GMPS and MOCOS were associated with azathioprineinduced

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.