These results suggest that NUDT15 R139C-related thiopurine-induced leukocytopenia is mediated by a 6-TGN-independent mechanism.

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The outcome of antiviral therapy is associated with viral and host factors. In the present study, the association between MHC class I-related chain B () genotypes and therapeutic response to pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy was investigated in hepatitis C virus (HCV)-infected patients. In total, 107 patients with chronic HCV infection (74 with HCV serotype 1 and 33 with serotype 2) were enrolled. Genotyping of single-nucleotide polymorphism (SNP) rs3828913 and interleukin-28B () SNP rs8099917 was performed using TaqMan SNP genotyping assays. The genotype distribution of the alleles was: CC, 79.4%; CA, 17.8%; and AA, 2.8%. Sustained virological response (SVR) was achieved by 55.1% (59/107) of the HCV patients. The SVR rate of patients with major (CC) alleles was 62.3% and this rate was significantly higher than that of the patients with minor (CA and AA) alleles (27.2%) (P=0.0068). A multivariate logistic model showed that the major genotype was an independent factor contributing to SVR (OR, 4.47; 95% CI, 1.46-13.70; P=0.009). In addition, the genotype was identified as the sole independent factor contributing to SVR and non-virological response in HCV serotype 1 patients with the major genotype. In HCV serotype 2 patients, the genotype was the sole significant factor contributing to SVR (OR, 30.68; 95% CI, 2.72-346.3; P=0.006). In conclusion, the genotype is a strong predictive factor for virological response to PEG-IFN/RBV therapy in HCV patients.

We previously demonstrated that per os administration and ad libitum ingestion of a magnesium chloride (MgCl 2 ) solution had a prophylactic effect on dextran sulfate sodium (DSS)-induced colitis in mice, magnesium being considered to play a role in this preferable action. Magnesium oxide (MgO) is a commercially available magnesium formulation, but whether or not it prevents development of colitis is unknown. In this study, we investigated the effect of MgO administration on development of colitis in DSS-treated male C57BL/6J mice. Experimental colitis was induced by ad libitum ingestion of 1% (w/v) DSS, and the colitis severity was evaluated by disease activity index (DAI) scores, histological assessment and colonic expression of inflammatory cytokines. A 1 mg/mL MgO solution was administered to mice through ad libitum ingestion from a day before DSS treatment to the end of the experimental period of 12 d. In addition, the effects of DSS, MgO and their combination on the gut microbiota were investigated by 16S ribosomal RNA metagenome analysis. DSS-induced elevation of DAI scores was partially but significantly decreased by MgO administration, while MgO administration had no apparent effect on the shortened colonic length, elevated mRNA expression of colonic interleukin-1β and tumor necrosis factor-α, increased accumulation of colonic mast cells, or altered features of the gut microbiota in DSS-treated mice. Overall, we demonstrated that MgO had a prophylactic effect on the development of colitis in DSS-treated mice by preventing histological colonic damage, but not colonic inflammation or alteration of the gut microbiota.