Combining clinical and candidate gene data into a risk score for azathioprine-associated leukopenia in routine clinical practice.
Pharmacogenomics J
; 20(5): 736-745, 2020 10.
Article
in En
| MEDLINE
| ID: mdl-32054992
ABSTRACT
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.
Full text:
1
Database:
MEDLINE
Main subject:
Azathioprine
/
Polymorphism, Single Nucleotide
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Pharmacogenomic Variants
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Immunosuppressive Agents
/
Leukopenia
/
Methyltransferases
Type of study:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Pharmacogenomics J
Journal subject:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Year:
2020
Type:
Article
Affiliation country:
United States