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BackgroundThe impact of genetic variation in thethiopurine S-methyltransferase (TPMT)gene on thiopurine-induced leukopenia has been well demonstrated. Although xanthine dehydrogenase (XDH)is the second major contributor to azathioprine breakdown, polymorphisms inXDHhave rarely been studied in IBD patients. We aim to access association betweenXDHvariants and thiopurine-induced leukopenia by gene–gene interaction in a Crohn’s disease (CD) population.StudyA total of 964 CD patients treated with thiopurines were recruited from a tertiary referral center. The association between fourXDHvariants (p.Gly172Arg, p.Asn1109Thr, p.Arg149Cys, and p.Thr910Lys) and thiopurine-induced leukopenia was analyzed in cases with early leukopenia (n = 66), late leukopenia (n = 264), and in controls without leukopenia (n = 632). Three non-synonymous SNPs, which we previously reported association with thiopurine-induced leukopenia,NUDT15(p.Arg139Cys),SUCLA2(p.Ser199Thr), andTPMT *3Cwere selected for epistasis analysis with theXDHvariants.ResultsThere was no significant association for two variants ofXDHand thiopurine-induced leukopenia. In the epistasis analysis, onlyXDH(p.Asn1109Thr) *SUCLA2(p.Ser199Thr) showed a statistically significant association with early leukopenia [odds ratio (OR) = 0.16;p = 0.03]. After genotype stratification, a positive association on the background ofSUCLA2wild-type (199Ser) between theXDH(p.Asn1109Thr) and early leukopenia (OR = 4.39;p = 0.01) was detected.ConclusionGenes associated with thiopurine-induced leukopenia can act in a complex interactive manner. Further studies are warranted to explore the mechanisms underlying the effects of the combination ofXDH(p.Asn1109Thr) andSUCLA2(199Ser) on thiopurine-induced leukopenia. [ABSTRACT FROM PUBLISHER]

Objective. The long-term efficacy of azathioprine (AZA) in steroid-dependent ulcerative colitis (UC) is still unclear. We aimed to evaluate the efficacy of AZA in patients with steroid-dependent UC. Material and methods. We retrospectively reviewed die medical records of 106 patients with steroid-dependent UC who were administered AZA. Three-year outcomes of AZA therapy were evaluated. The outcome of the treatment was defined as (1) success, indicating induction and maintenance of remission throughout the study period (complete success) or remission followed by infrequent and short relapses (partial success); or (2) failure, indicating the absence of remission, frequent or prolonged relapses, infliximab administration, or colectomy. Results. Of the 106 patients, 73 (68.9%) continued on AZA for >6 months (AZA therapy group) and 33 (31.1%) discontinued AZA within 6 months due to intolerance (AZA intolerance group, n = 20), colectomy (n = 6), or follow-up loss (n = 7). Three-year outcomes for 106 patients were success in 54.7% (complete success, 35.8%; partial success, 18.9%), failure in 32.1% (frequent or prolonged relapses, 12.3%; infliximab administration, 5.6%; colectomy, 14.2%), and follow-up loss or death in 13.2%. The success rate increased to 71.2% (complete success, 46.6%; partial success, 24.7%) when the analysis was confined to the 73 patients who continued AZA for > 6 months. The 3-year success rate was higher in the AZA therapy group (71.2%) than the AZA intolerance group (25.0%) (p < 0.001). Conclusions. AZA is an effective treatment for steroid-dependent UC. The efficacy of AZA is well sustained over 3 years. [ABSTRACT FROM AUTHOR]