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Influence of NUDT15 variants on hematological pictures of patients with inflammatory bowel disease treated with thiopurines

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World Journal of Gastroenterology 2018年第4期24卷 511-518页

作者： Yuichiro Kojima yosuke hirotsu Wataru Omata Makoto Sugimori Shinya Takaoka Hiroshi Ashizawa Keiko Nakagomi Dai Yoshimura Kenji Hosoda Yoji Suzuki Hitoshi Mochizuki Masao Omata Department of Gastroenterology Yamanashi Prefectural Central Hospital Genome Analysis Center Yamanashi Prefectural Central Hospital Department of Dermatologic Oncology National Cancer Institute Division of Gastroenterology Department of Medicine Yokohama City University Graduate School of Medicine Department of Gastroenterology Genome Analysis Center Yamanashi Prefectural Central Hospital

AIM The single nucleotide polymorphism(SNP) c.415C>T in exon 3 of NUDT15 affects thiopurine-induced leukopenia in Asian patients with Crohn's disease. Meanwhile, three additional genetic variants of NUDT15 were reported in patients with acute lymphoblastic leukemia. We evaluated the effects of these additional genetic variants of NUDT15 in patients with inflammatory bowel disease(IBD) treated with *** Ninety-six Japanese patients with IBD were enrolled. Genotyping for the NUDT15 and TPMT genes was performed using Custom Taq Man SNP genotyping assays or Sanger sequencing. The changes in white blood cell(WBC) count, mean corpuscular volume(MCV), platelet count, hemoglobin, CRP, amylase, albumin, AST, ALT, and ESR were *** Genetic variants of exon 1 and exon 3 of NUDT15 were identified in 24 of 96 patients(25.0%). C.52G > A and c.36_37 insG GAGTC in exon 1 were found in three patients each. All three patients with c.36_37 insG GAGTC in exon 1 were heterozygotes of ***139 Cys in exon 3. Eighteen patients had ***139 Cys in exon 3 alone. The WBC count gradually decreased after initiation of thiopurine treatment in the mutated cases(n = 24), and was significantly lower at 6, 8, 10, and 16 wk(P = 0.0271, 0.0037, 0.0051, and 0.0185, respectively). The WBC counts were also evaluated in patients with and without prednisolone treatment. In the patients with prednisolone treatment, the WBC count tended to show a greater decrease in the mutated cases, with significant differences at 8 and 10 wk(P = 0.012 and 0.029, respectively). In the patients without prednisolone treatment, the WBC count was significantly lower at 2, 4, 8, and 14 wk in mutated cases(P = 0.0196, 0.0182, 0.0237 and 0.0241, respectively). MCV increased after starting thiopurine treatment in the mutated cases, and was significantly higher at 10 wk(P = 0.0085). Platelet count, hemoglobin, CRP, amylase, albumin, AST, ALT and ESR did not differ significantly between the wildtype and

关键词： Inflammatory bowel disease NUDT15 Leukopenia Mean corpuscular volume Japanese

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