Combining clinical and candidate gene data into a risk score for azathioprine-associated leukopenia in routine clinical practice
Leukopenia is a serious, frequent side effect associated with azathioprine use. Currently, we use thiopurine methyltransferase (TPMT) testing to predict leukopenia in patients taking azathioprine. We hypothesized that a risk score incorporating additional clinical and genetic variables would improve the prediction of azathioprine-associated leukopenia. In the discovery phase, we developed four risk score models: (1) age, sex, and TPMT metabolizer status; (2) model 1 plus additional clinical variables; (3) sixty candidate single nucleotide polymorphisms; and (4) model 2 plus model 3. The area under the receiver-operating-characteristic curve (AUC) of the risk scores was 0.59 (95% CI: 0.54-0.64), 0.75 (0.71-0.80), 0.66 (0.61-0.71), and 0.78 (0.74-0.82) for models 1, 2, 3, and 4, respectively. During the replication phase, models 2 and 4 (AUC = 0.64, 95% CI: 0.59-0.70 and AUC = 0.63, 95% CI: 0.58-0.69, respectively) were significant in an independent group. Compared with TPMT testing alone, additional genetic and clinical variables improve the prediction of azathioprine-associated leukopenia.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
The pharmacogenomics journal - 20(2020), 5 vom: 13. Okt., Seite 736-745 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Anandi, Prathima [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 07.07.2021 Date Revised 03.08.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41397-020-0163-4 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM306491915 |
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| 100 | 1 | |a Anandi, Prathima |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Combining clinical and candidate gene data into a risk score for azathioprine-associated leukopenia in routine clinical practice |
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| 520 | |a Leukopenia is a serious, frequent side effect associated with azathioprine use. Currently, we use thiopurine methyltransferase (TPMT) testing to predict leukopenia in patients taking azathioprine. We hypothesized that a risk score incorporating additional clinical and genetic variables would improve the prediction of azathioprine-associated leukopenia. In the discovery phase, we developed four risk score models: (1) age, sex, and TPMT metabolizer status; (2) model 1 plus additional clinical variables; (3) sixty candidate single nucleotide polymorphisms; and (4) model 2 plus model 3. The area under the receiver-operating-characteristic curve (AUC) of the risk scores was 0.59 (95% CI: 0.54-0.64), 0.75 (0.71-0.80), 0.66 (0.61-0.71), and 0.78 (0.74-0.82) for models 1, 2, 3, and 4, respectively. During the replication phase, models 2 and 4 (AUC = 0.64, 95% CI: 0.59-0.70 and AUC = 0.63, 95% CI: 0.58-0.69, respectively) were significant in an independent group. Compared with TPMT testing alone, additional genetic and clinical variables improve the prediction of azathioprine-associated leukopenia | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Dickson, Alyson L |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, QiPing |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Wei-Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Dupont, William D |e verfasserin |4 aut | |
| 700 | 1 | |a Plummer, Dale |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Ge |e verfasserin |4 aut | |
| 700 | 1 | |a Octaria, Rany |e verfasserin |4 aut | |
| 700 | 1 | |a Barker, Katherine A |e verfasserin |4 aut | |
| 700 | 1 | |a Kawai, Vivian K |e verfasserin |4 aut | |
| 700 | 1 | |a Birdwell, Kelly |e verfasserin |4 aut | |
| 700 | 1 | |a Cox, Nancy J |e verfasserin |4 aut | |
| 700 | 1 | |a Hung, Adriana |e verfasserin |4 aut | |
| 700 | 1 | |a Stein, C Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Chung, Cecilia P |e verfasserin |4 aut | |
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