The Experts below are selected from a list of 282 Experts worldwide ranked by ideXlab platform
Takahiko Toyonaga - One of the best experts on this subject based on the ideXlab platform.
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NUDT15 codon 139 is the best pharmacogenetic marker for predicting thiopurine-induced severe adverse events in Japanese patients with inflammatory bowel disease: a multicenter study
Journal of Gastroenterology, 2018Co-Authors: Yoichi Kakuta, Kentaro Ikeya, Hirotake Sakuraba, Shoko Nakagawa, Tetsuya Takagawa, Daisuke Okamoto, Yosuke Kawai, Miki Miura, Atsushi Nishida, Takahiko ToyonagaAbstract:Background Despite NUDT15 variants showing significant association with thiopurine-induced adverse events (AEs) in Asians, it remains unclear which variants of NUDT15 or whether additional genetic variants should be tested to predict AEs. To clarify the best pharmacogenetic test to be used clinically, we performed association studies of NUDT15 variants and haplotypes with AEs, genome-wide association study (GWAS) to discover additional variants, and ROC analysis to select the model to predict severe AEs. Methods Overall, 2630 patients with inflammatory bowel disease (IBD) were enrolled and genotyped for NUDT15 codon 139; 1291 patients were treated with thiopurines. diplotypes were analyzed in 970 patients, and GWASs of AEs were performed with 1221 patients using population-optimized genotyping array and imputation. Results We confirmed the association of NUDT15 p.Arg139Cys with Leukopenia and alopecia ( p = 2.20E−63, 1.32E−69, OR = 6.59, 12.1, respectively), and found a novel association with digestive symptoms ( p = 6.39E−04, OR = 1.89). Time to Leukopenia was significantly shorter, and when Leukopenia was diagnosed, thiopurine doses were significantly lower in Arg/Cys and Cys/Cys than in Arg/Arg. In GWASs, no additional variants were found to be associated with thiopurine-induced AEs. Despite strong correlation of Leukopenia frequency with estimated enzyme activities based on the diplotypes ( r ^2 = 0.926, p = 0.0087), there were no significant differences in the AUCs of diplotypes from those of codon 139 to predict severe AEs (AUC = 0.916, 0.921, for acute severe Leukopenia, AUC = 0.990, 0.991, for severe alopecia, respectively). Conclusions Genotyping of NUDT15 codon 139 was sufficient to predict acute severe Leukopenia and alopecia in Japanese patients with IBD.
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nudt15 codon 139 is the best pharmacogenetic marker for predicting thiopurine induced severe adverse events in japanese patients with inflammatory bowel disease a multicenter study
Journal of Gastroenterology, 2018Co-Authors: Yoichi Kakuta, Kentaro Ikeya, Hirotake Sakuraba, Shoko Nakagawa, Tetsuya Takagawa, Daisuke Okamoto, Yosuke Kawai, Miki Miura, Atsushi Nishida, Takahiko ToyonagaAbstract:Despite NUDT15 variants showing significant association with thiopurine-induced adverse events (AEs) in Asians, it remains unclear which variants of NUDT15 or whether additional genetic variants should be tested to predict AEs. To clarify the best pharmacogenetic test to be used clinically, we performed association studies of NUDT15 variants and haplotypes with AEs, genome-wide association study (GWAS) to discover additional variants, and ROC analysis to select the model to predict severe AEs. Overall, 2630 patients with inflammatory bowel disease (IBD) were enrolled and genotyped for NUDT15 codon 139; 1291 patients were treated with thiopurines. diplotypes were analyzed in 970 patients, and GWASs of AEs were performed with 1221 patients using population-optimized genotyping array and imputation. We confirmed the association of NUDT15 p.Arg139Cys with Leukopenia and alopecia (p = 2.20E−63, 1.32E−69, OR = 6.59, 12.1, respectively), and found a novel association with digestive symptoms (p = 6.39E−04, OR = 1.89). Time to Leukopenia was significantly shorter, and when Leukopenia was diagnosed, thiopurine doses were significantly lower in Arg/Cys and Cys/Cys than in Arg/Arg. In GWASs, no additional variants were found to be associated with thiopurine-induced AEs. Despite strong correlation of Leukopenia frequency with estimated enzyme activities based on the diplotypes (r2 = 0.926, p = 0.0087), there were no significant differences in the AUCs of diplotypes from those of codon 139 to predict severe AEs (AUC = 0.916, 0.921, for acute severe Leukopenia, AUC = 0.990, 0.991, for severe alopecia, respectively). Genotyping of NUDT15 codon 139 was sufficient to predict acute severe Leukopenia and alopecia in Japanese patients with IBD.
Yoichi Kakuta - One of the best experts on this subject based on the ideXlab platform.
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NUDT15 codon 139 is the best pharmacogenetic marker for predicting thiopurine-induced severe adverse events in Japanese patients with inflammatory bowel disease: a multicenter study
Journal of Gastroenterology, 2018Co-Authors: Yoichi Kakuta, Kentaro Ikeya, Hirotake Sakuraba, Shoko Nakagawa, Tetsuya Takagawa, Daisuke Okamoto, Yosuke Kawai, Miki Miura, Atsushi Nishida, Takahiko ToyonagaAbstract:Background Despite NUDT15 variants showing significant association with thiopurine-induced adverse events (AEs) in Asians, it remains unclear which variants of NUDT15 or whether additional genetic variants should be tested to predict AEs. To clarify the best pharmacogenetic test to be used clinically, we performed association studies of NUDT15 variants and haplotypes with AEs, genome-wide association study (GWAS) to discover additional variants, and ROC analysis to select the model to predict severe AEs. Methods Overall, 2630 patients with inflammatory bowel disease (IBD) were enrolled and genotyped for NUDT15 codon 139; 1291 patients were treated with thiopurines. diplotypes were analyzed in 970 patients, and GWASs of AEs were performed with 1221 patients using population-optimized genotyping array and imputation. Results We confirmed the association of NUDT15 p.Arg139Cys with Leukopenia and alopecia ( p = 2.20E−63, 1.32E−69, OR = 6.59, 12.1, respectively), and found a novel association with digestive symptoms ( p = 6.39E−04, OR = 1.89). Time to Leukopenia was significantly shorter, and when Leukopenia was diagnosed, thiopurine doses were significantly lower in Arg/Cys and Cys/Cys than in Arg/Arg. In GWASs, no additional variants were found to be associated with thiopurine-induced AEs. Despite strong correlation of Leukopenia frequency with estimated enzyme activities based on the diplotypes ( r ^2 = 0.926, p = 0.0087), there were no significant differences in the AUCs of diplotypes from those of codon 139 to predict severe AEs (AUC = 0.916, 0.921, for acute severe Leukopenia, AUC = 0.990, 0.991, for severe alopecia, respectively). Conclusions Genotyping of NUDT15 codon 139 was sufficient to predict acute severe Leukopenia and alopecia in Japanese patients with IBD.
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nudt15 codon 139 is the best pharmacogenetic marker for predicting thiopurine induced severe adverse events in japanese patients with inflammatory bowel disease a multicenter study
Journal of Gastroenterology, 2018Co-Authors: Yoichi Kakuta, Kentaro Ikeya, Hirotake Sakuraba, Shoko Nakagawa, Tetsuya Takagawa, Daisuke Okamoto, Yosuke Kawai, Miki Miura, Atsushi Nishida, Takahiko ToyonagaAbstract:Despite NUDT15 variants showing significant association with thiopurine-induced adverse events (AEs) in Asians, it remains unclear which variants of NUDT15 or whether additional genetic variants should be tested to predict AEs. To clarify the best pharmacogenetic test to be used clinically, we performed association studies of NUDT15 variants and haplotypes with AEs, genome-wide association study (GWAS) to discover additional variants, and ROC analysis to select the model to predict severe AEs. Overall, 2630 patients with inflammatory bowel disease (IBD) were enrolled and genotyped for NUDT15 codon 139; 1291 patients were treated with thiopurines. diplotypes were analyzed in 970 patients, and GWASs of AEs were performed with 1221 patients using population-optimized genotyping array and imputation. We confirmed the association of NUDT15 p.Arg139Cys with Leukopenia and alopecia (p = 2.20E−63, 1.32E−69, OR = 6.59, 12.1, respectively), and found a novel association with digestive symptoms (p = 6.39E−04, OR = 1.89). Time to Leukopenia was significantly shorter, and when Leukopenia was diagnosed, thiopurine doses were significantly lower in Arg/Cys and Cys/Cys than in Arg/Arg. In GWASs, no additional variants were found to be associated with thiopurine-induced AEs. Despite strong correlation of Leukopenia frequency with estimated enzyme activities based on the diplotypes (r2 = 0.926, p = 0.0087), there were no significant differences in the AUCs of diplotypes from those of codon 139 to predict severe AEs (AUC = 0.916, 0.921, for acute severe Leukopenia, AUC = 0.990, 0.991, for severe alopecia, respectively). Genotyping of NUDT15 codon 139 was sufficient to predict acute severe Leukopenia and alopecia in Japanese patients with IBD.
Yves Gillet - One of the best experts on this subject based on the ideXlab platform.
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Severe Leukopenia in Staphylococcus aureus-necrotizing, community-acquired pneumonia: risk factors and impact on survival.
BMC Infectious Diseases, 2013Co-Authors: Nagham Khanafer, Nicolas Sicot, Philippe Vanhems, Oana Dumitrescu, Vanina Meyssonier, Anne Tristan, Michèle Bès, Gérard Lina, François Vandenesch, Yves GilletAbstract:BACKGROUND: Necrotizing pneumonia attributed to Panton-Valentine leukocidin-positive Staphylococcus aureus has mainly been reported in otherwise healthy children and young adults, with a high mortality rate. Erythroderma, airway bleeding, and Leukopenia have been shown to be predictive of mortality. The objectives of this study were to define the characteristics of patients with severe Leukopenia at 48-h hospitalization and to update our data regarding mortality predicting factors in a larger population than we had previously described. METHODS: It was designed as a case-case study nested in a cohort study. A total of 148 cases of community-acquired, necrotizing pneumonia were included. The following data were collected: basic demographic information, medical history, signs and symptoms, radiological findings and laboratory results during the first 48 h of hospitalization. The study population was divided into 2 groups: (1) with severe Leukopenia (leukocyte count ≤3,000 leukocytes/mL, n=62) and (2) without severe Leukopenia (>3,000 leukocytes/mL, n=86). RESULTS: Median age was 22 years, and the male-to-female gender ratio was 1.5. The overall in-hospital mortality rate was 41.2%. Death occurred in 75.8% of severe Leukopenia cases with median survival time of 4 days, and in 16.3% of cases with leukocyte count >3,000/mL (P
Daisuke Okamoto - One of the best experts on this subject based on the ideXlab platform.
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NUDT15 codon 139 is the best pharmacogenetic marker for predicting thiopurine-induced severe adverse events in Japanese patients with inflammatory bowel disease: a multicenter study
Journal of Gastroenterology, 2018Co-Authors: Yoichi Kakuta, Kentaro Ikeya, Hirotake Sakuraba, Shoko Nakagawa, Tetsuya Takagawa, Daisuke Okamoto, Yosuke Kawai, Miki Miura, Atsushi Nishida, Takahiko ToyonagaAbstract:Background Despite NUDT15 variants showing significant association with thiopurine-induced adverse events (AEs) in Asians, it remains unclear which variants of NUDT15 or whether additional genetic variants should be tested to predict AEs. To clarify the best pharmacogenetic test to be used clinically, we performed association studies of NUDT15 variants and haplotypes with AEs, genome-wide association study (GWAS) to discover additional variants, and ROC analysis to select the model to predict severe AEs. Methods Overall, 2630 patients with inflammatory bowel disease (IBD) were enrolled and genotyped for NUDT15 codon 139; 1291 patients were treated with thiopurines. diplotypes were analyzed in 970 patients, and GWASs of AEs were performed with 1221 patients using population-optimized genotyping array and imputation. Results We confirmed the association of NUDT15 p.Arg139Cys with Leukopenia and alopecia ( p = 2.20E−63, 1.32E−69, OR = 6.59, 12.1, respectively), and found a novel association with digestive symptoms ( p = 6.39E−04, OR = 1.89). Time to Leukopenia was significantly shorter, and when Leukopenia was diagnosed, thiopurine doses were significantly lower in Arg/Cys and Cys/Cys than in Arg/Arg. In GWASs, no additional variants were found to be associated with thiopurine-induced AEs. Despite strong correlation of Leukopenia frequency with estimated enzyme activities based on the diplotypes ( r ^2 = 0.926, p = 0.0087), there were no significant differences in the AUCs of diplotypes from those of codon 139 to predict severe AEs (AUC = 0.916, 0.921, for acute severe Leukopenia, AUC = 0.990, 0.991, for severe alopecia, respectively). Conclusions Genotyping of NUDT15 codon 139 was sufficient to predict acute severe Leukopenia and alopecia in Japanese patients with IBD.
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nudt15 codon 139 is the best pharmacogenetic marker for predicting thiopurine induced severe adverse events in japanese patients with inflammatory bowel disease a multicenter study
Journal of Gastroenterology, 2018Co-Authors: Yoichi Kakuta, Kentaro Ikeya, Hirotake Sakuraba, Shoko Nakagawa, Tetsuya Takagawa, Daisuke Okamoto, Yosuke Kawai, Miki Miura, Atsushi Nishida, Takahiko ToyonagaAbstract:Despite NUDT15 variants showing significant association with thiopurine-induced adverse events (AEs) in Asians, it remains unclear which variants of NUDT15 or whether additional genetic variants should be tested to predict AEs. To clarify the best pharmacogenetic test to be used clinically, we performed association studies of NUDT15 variants and haplotypes with AEs, genome-wide association study (GWAS) to discover additional variants, and ROC analysis to select the model to predict severe AEs. Overall, 2630 patients with inflammatory bowel disease (IBD) were enrolled and genotyped for NUDT15 codon 139; 1291 patients were treated with thiopurines. diplotypes were analyzed in 970 patients, and GWASs of AEs were performed with 1221 patients using population-optimized genotyping array and imputation. We confirmed the association of NUDT15 p.Arg139Cys with Leukopenia and alopecia (p = 2.20E−63, 1.32E−69, OR = 6.59, 12.1, respectively), and found a novel association with digestive symptoms (p = 6.39E−04, OR = 1.89). Time to Leukopenia was significantly shorter, and when Leukopenia was diagnosed, thiopurine doses were significantly lower in Arg/Cys and Cys/Cys than in Arg/Arg. In GWASs, no additional variants were found to be associated with thiopurine-induced AEs. Despite strong correlation of Leukopenia frequency with estimated enzyme activities based on the diplotypes (r2 = 0.926, p = 0.0087), there were no significant differences in the AUCs of diplotypes from those of codon 139 to predict severe AEs (AUC = 0.916, 0.921, for acute severe Leukopenia, AUC = 0.990, 0.991, for severe alopecia, respectively). Genotyping of NUDT15 codon 139 was sufficient to predict acute severe Leukopenia and alopecia in Japanese patients with IBD.
Atsushi Nishida - One of the best experts on this subject based on the ideXlab platform.
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NUDT15 codon 139 is the best pharmacogenetic marker for predicting thiopurine-induced severe adverse events in Japanese patients with inflammatory bowel disease: a multicenter study
Journal of Gastroenterology, 2018Co-Authors: Yoichi Kakuta, Kentaro Ikeya, Hirotake Sakuraba, Shoko Nakagawa, Tetsuya Takagawa, Daisuke Okamoto, Yosuke Kawai, Miki Miura, Atsushi Nishida, Takahiko ToyonagaAbstract:Background Despite NUDT15 variants showing significant association with thiopurine-induced adverse events (AEs) in Asians, it remains unclear which variants of NUDT15 or whether additional genetic variants should be tested to predict AEs. To clarify the best pharmacogenetic test to be used clinically, we performed association studies of NUDT15 variants and haplotypes with AEs, genome-wide association study (GWAS) to discover additional variants, and ROC analysis to select the model to predict severe AEs. Methods Overall, 2630 patients with inflammatory bowel disease (IBD) were enrolled and genotyped for NUDT15 codon 139; 1291 patients were treated with thiopurines. diplotypes were analyzed in 970 patients, and GWASs of AEs were performed with 1221 patients using population-optimized genotyping array and imputation. Results We confirmed the association of NUDT15 p.Arg139Cys with Leukopenia and alopecia ( p = 2.20E−63, 1.32E−69, OR = 6.59, 12.1, respectively), and found a novel association with digestive symptoms ( p = 6.39E−04, OR = 1.89). Time to Leukopenia was significantly shorter, and when Leukopenia was diagnosed, thiopurine doses were significantly lower in Arg/Cys and Cys/Cys than in Arg/Arg. In GWASs, no additional variants were found to be associated with thiopurine-induced AEs. Despite strong correlation of Leukopenia frequency with estimated enzyme activities based on the diplotypes ( r ^2 = 0.926, p = 0.0087), there were no significant differences in the AUCs of diplotypes from those of codon 139 to predict severe AEs (AUC = 0.916, 0.921, for acute severe Leukopenia, AUC = 0.990, 0.991, for severe alopecia, respectively). Conclusions Genotyping of NUDT15 codon 139 was sufficient to predict acute severe Leukopenia and alopecia in Japanese patients with IBD.
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nudt15 codon 139 is the best pharmacogenetic marker for predicting thiopurine induced severe adverse events in japanese patients with inflammatory bowel disease a multicenter study
Journal of Gastroenterology, 2018Co-Authors: Yoichi Kakuta, Kentaro Ikeya, Hirotake Sakuraba, Shoko Nakagawa, Tetsuya Takagawa, Daisuke Okamoto, Yosuke Kawai, Miki Miura, Atsushi Nishida, Takahiko ToyonagaAbstract:Despite NUDT15 variants showing significant association with thiopurine-induced adverse events (AEs) in Asians, it remains unclear which variants of NUDT15 or whether additional genetic variants should be tested to predict AEs. To clarify the best pharmacogenetic test to be used clinically, we performed association studies of NUDT15 variants and haplotypes with AEs, genome-wide association study (GWAS) to discover additional variants, and ROC analysis to select the model to predict severe AEs. Overall, 2630 patients with inflammatory bowel disease (IBD) were enrolled and genotyped for NUDT15 codon 139; 1291 patients were treated with thiopurines. diplotypes were analyzed in 970 patients, and GWASs of AEs were performed with 1221 patients using population-optimized genotyping array and imputation. We confirmed the association of NUDT15 p.Arg139Cys with Leukopenia and alopecia (p = 2.20E−63, 1.32E−69, OR = 6.59, 12.1, respectively), and found a novel association with digestive symptoms (p = 6.39E−04, OR = 1.89). Time to Leukopenia was significantly shorter, and when Leukopenia was diagnosed, thiopurine doses were significantly lower in Arg/Cys and Cys/Cys than in Arg/Arg. In GWASs, no additional variants were found to be associated with thiopurine-induced AEs. Despite strong correlation of Leukopenia frequency with estimated enzyme activities based on the diplotypes (r2 = 0.926, p = 0.0087), there were no significant differences in the AUCs of diplotypes from those of codon 139 to predict severe AEs (AUC = 0.916, 0.921, for acute severe Leukopenia, AUC = 0.990, 0.991, for severe alopecia, respectively). Genotyping of NUDT15 codon 139 was sufficient to predict acute severe Leukopenia and alopecia in Japanese patients with IBD.