RESUMEN
BACKGROUND/AIMS: Recent genome-wide analyses have provided strong evidence concerning adverse events caused by thiopurine drugs such as azathioprine (AZA) and 6-mercaptopurine. The strong associations identified between NUDT15 p.Arg139Cys and thiopurine-induced leukopenia and severe hair loss have been studied and confirmed over the last 2 years. However, other coding variants, including NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, and FTO p.Ala134Thr, and a noncoding variation in RUNX1 (rs2834826) remain to be examined in detail in this respect. Therefore, we investigated the correlation between these adverse events and the 5 recently identified variants mentioned above among Japanese patients with inflammatory bowel diseases (IBD). METHODS: One hundred sixty thiopurine-treated patients with IBD were enrolled. Genotyping was performed using TaqMan SNP Genotyping Assays or Sanger sequencing. RESULTS: None of the 5 variants were associated with gastrointestinal intolerance to AZA. However, NUDT15 p.Arg139Cys was significantly associated with the interval between initiation and discontinuation of AZA among patients with gastrointestinal intolerance. This variant was strongly associated with early (<8 weeks) and late (≥8 weeks) leukopenia and severe hair loss. Moreover, it correlated with the interval between initiation of thiopurine therapy and leukopenia occurrence, and average thiopurine dose. NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, FTO p.Ala134Thr, and RUNX1 rs2834826 exhibited no significant relationship with the adverse events examined. CONCLUSIONS: Of the 5 variants investigated, NUDT15 p.Arg139Cys had the strongest impact on thiopurine-induced leukopenia and severe hair loss; therefore, its genotyping should be prioritized over that of other variants in efforts to predict these adverse events in Japanese patients with IBD.
Asunto(s)
Humanos , Mercaptopurina , Pueblo Asiatico , Azatioprina , Codificación Clínica , Cabello , Enfermedades Inflamatorias del Intestino , LeucopeniaRESUMEN
BACKGROUND/AIMS: Epidemiological studies suggest that there is a considerable overlap between functional dyspepsia (FD) and irritable bowel syndrome (IBS). The aim of this study was to examine concurrent gastrointestinal symptoms in FD and IBS. METHODS: A total of 186 college students filled out a questionnaire regarding whether they had uninvestigated dyspepsia (UD, FD without endoscopic examination) and IBS based on Rome-II criteria. Gastrointestinal symptoms were measured using the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. RESULTS: A total of 181 students (98 males, mean age 24.6 years) completed both questionnaires. The prevalence of UD, IBS, and UD+IBS overlap was 12 (6.7%), 40 (22.1%), and 8 (4.4%), respectively. A significant UD+IBS overlap was observed (66.7% IBS in UD, 20.0% UD in IBS). Reflux scores of GSRS in either UD or IBS were significantly greater than in those without. Gastroesophageal reflux disease (GERD), defined as weekly occurring moderate symptoms of heartburn and/or acid regurgitation and evaluated using the GSRS, was found in 16 (8.8%) of the subjects. The prevalence of IBS was significantly higher in GERD patients than in non-GERD patients (50.0% vs 19.4%). CONCLUSIONS: The considerable overlap not only between UD and IBS, but also between GERD and IBS, suggests the involvement of common pathophysiological disturbances in the two conditions.