Dutch pharmacogenetics working group guideline for the gene-drug interaction of ABCG2, HLA-B and Allopurinol, and MTHFR, folic acid and methotrexate
© 2022. The Author(s), under exclusive licence to European Society of Human Genetics..
The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate PGx implementation by developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy. This guideline describes the gene-drug interaction of ABCG2 with allopurinol, HLA-B with allopurinol, MTHFR with folic acid, and MTHFR with methotrexate, relevant for the treatment of gout, cancer, and rheumatoid arthritis. A systematic review was performed based on which pharmacotherapeutic recommendations were developed. Allopurinol is less effective in patients with the ABCG2 p.(Gln141Lys) variant. In HLA-B*58:01 carriers, the risk of severe cutaneous adverse events associated with allopurinol is strongly increased. The DPWG recommends using a higher allopurinol dose in patients with the ABCG2 p.(Gln141Lys) variant. For HLA-B*58:01 positive patients the DPWG recommends choosing an alternative (for instance febuxostat). The DPWG indicates that another option would be to precede treatment with allopurinol tolerance induction. Genotyping of ABCG2 in patients starting on allopurinol was judged to be 'potentially beneficial' for drug effectiveness, meaning genotyping can be considered on an individual patient basis. Genotyping for HLA-B*58:01 in patients starting on allopurinol was judged to be 'beneficial' for drug safety, meaning it is advised to consider genotyping the patient before (or directly after) drug therapy has been initiated. For MTHFR-folic acid there is evidence for a gene-drug interaction, but there is insufficient evidence for a clinical effect that makes therapy adjustment useful. Finally, for MTHFR-methotrexate there is insufficient evidence for a gene-drug interaction.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:32 |
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| Enthalten in: |
European journal of human genetics : EJHG - 32(2024), 2 vom: 02. Feb., Seite 155-162 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
van der Pol, Karel H [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.02.2024 Date Revised 21.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41431-022-01180-0 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate PGx implementation by developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy. This guideline describes the gene-drug interaction of ABCG2 with allopurinol, HLA-B with allopurinol, MTHFR with folic acid, and MTHFR with methotrexate, relevant for the treatment of gout, cancer, and rheumatoid arthritis. A systematic review was performed based on which pharmacotherapeutic recommendations were developed. Allopurinol is less effective in patients with the ABCG2 p.(Gln141Lys) variant. In HLA-B*58:01 carriers, the risk of severe cutaneous adverse events associated with allopurinol is strongly increased. The DPWG recommends using a higher allopurinol dose in patients with the ABCG2 p.(Gln141Lys) variant. For HLA-B*58:01 positive patients the DPWG recommends choosing an alternative (for instance febuxostat). The DPWG indicates that another option would be to precede treatment with allopurinol tolerance induction. Genotyping of ABCG2 in patients starting on allopurinol was judged to be 'potentially beneficial' for drug effectiveness, meaning genotyping can be considered on an individual patient basis. Genotyping for HLA-B*58:01 in patients starting on allopurinol was judged to be 'beneficial' for drug safety, meaning it is advised to consider genotyping the patient before (or directly after) drug therapy has been initiated. For MTHFR-folic acid there is evidence for a gene-drug interaction, but there is insufficient evidence for a clinical effect that makes therapy adjustment useful. Finally, for MTHFR-methotrexate there is insufficient evidence for a gene-drug interaction | ||
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| 700 | 1 | |a Soree, Bianca |e verfasserin |4 aut | |
| 700 | 1 | |a de Boer-Veger, Nienke J |e verfasserin |4 aut | |
| 700 | 1 | |a Buunk, Anne Marie |e verfasserin |4 aut | |
| 700 | 1 | |a Guchelaar, Henk-Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Risselada, Arne |e verfasserin |4 aut | |
| 700 | 1 | |a van Schaik, Ron H N |e verfasserin |4 aut | |
| 700 | 1 | |a Swen, Jesse J |e verfasserin |4 aut | |
| 700 | 1 | |a Touw, Daan |e verfasserin |4 aut | |
| 700 | 1 | |a van der Weide, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a van Westrhenen, Roos |e verfasserin |4 aut | |
| 700 | 1 | |a Deneer, Vera H M |e verfasserin |4 aut | |
| 700 | 1 | |a Houwink, Elisa J F |e verfasserin |4 aut | |
| 700 | 1 | |a Rongen, Gerard A |e verfasserin |4 aut | |
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