Genetic risk factors for clozapine-induced neutropenia and agranulocytosis in a Dutch psychiatric population
Prescription of clozapine is complicated by the occurrence of clozapine-induced reduction of neutrophils. The aim of this study was to identify genetic risk factors in a population of 310 Dutch patients treated with clozapine, including 38 patients developing neutropenia and 31 patients developing a...
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| Veröffentlicht in: | The Pharmacogenomics Journal 2017, Vol.17 (5), p.471 |
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| creator | van der Weide, K Loovers, H Pondman, K Bogers, J van der Straaten, T Langemeijer, E Cohen, D Commandeur, J van der Weide, J |
| description | Prescription of clozapine is complicated by the occurrence of clozapine-induced reduction of neutrophils. The aim of this study was to identify genetic risk factors in a population of 310 Dutch patients treated with clozapine, including 38 patients developing neutropenia and 31 patients developing agranulocytosis. NQO2 1541AA (NRH quinone oxidoreductase 2; protects cells against oxidative metabolites) was present at a higher frequency in agranulocytosis patients compared with control (23% versus 7%, P=0.03), as was ABCB1 (ABC-transporter-B1; drug efflux transporter) 3435TT (32% versus 20%, P=0.05). In patients developing neutropenia, ABCB1 3435TT and homozygosity for GSTT1[sup.null] (glutathione-S-transferase; conjugates reactive clozapine metabolites into glutathione) were more frequent compared with control (34% versus 20%, P=0.05 and 31% versus 14%, P=0.03), whereas GSTM1[sup.null] was less frequent in these patients (31% versus 52%, P=0.03). To investigate whether combinations of the identified genetic risk factors have a higher predictive value, should be confirmed in a larger case-control study. The Pharmacogenomics Journal (2017) 17, 471-478; doi: 10.1038/tpj.2016.32; published online 10 May 2016 |
| doi_str_mv | 10.1038/tpj.2016.32 |
| format | Report |
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The aim of this study was to identify genetic risk factors in a population of 310 Dutch patients treated with clozapine, including 38 patients developing neutropenia and 31 patients developing agranulocytosis. NQO2 1541AA (NRH quinone oxidoreductase 2; protects cells against oxidative metabolites) was present at a higher frequency in agranulocytosis patients compared with control (23% versus 7%, P=0.03), as was ABCB1 (ABC-transporter-B1; drug efflux transporter) 3435TT (32% versus 20%, P=0.05). In patients developing neutropenia, ABCB1 3435TT and homozygosity for GSTT1[sup.null] (glutathione-S-transferase; conjugates reactive clozapine metabolites into glutathione) were more frequent compared with control (34% versus 20%, P=0.05 and 31% versus 14%, P=0.03), whereas GSTM1[sup.null] was less frequent in these patients (31% versus 52%, P=0.03). To investigate whether combinations of the identified genetic risk factors have a higher predictive value, should be confirmed in a larger case-control study. 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The aim of this study was to identify genetic risk factors in a population of 310 Dutch patients treated with clozapine, including 38 patients developing neutropenia and 31 patients developing agranulocytosis. NQO2 1541AA (NRH quinone oxidoreductase 2; protects cells against oxidative metabolites) was present at a higher frequency in agranulocytosis patients compared with control (23% versus 7%, P=0.03), as was ABCB1 (ABC-transporter-B1; drug efflux transporter) 3435TT (32% versus 20%, P=0.05). In patients developing neutropenia, ABCB1 3435TT and homozygosity for GSTT1[sup.null] (glutathione-S-transferase; conjugates reactive clozapine metabolites into glutathione) were more frequent compared with control (34% versus 20%, P=0.05 and 31% versus 14%, P=0.03), whereas GSTM1[sup.null] was less frequent in these patients (31% versus 52%, P=0.03). To investigate whether combinations of the identified genetic risk factors have a higher predictive value, should be confirmed in a larger case-control study. 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The aim of this study was to identify genetic risk factors in a population of 310 Dutch patients treated with clozapine, including 38 patients developing neutropenia and 31 patients developing agranulocytosis. NQO2 1541AA (NRH quinone oxidoreductase 2; protects cells against oxidative metabolites) was present at a higher frequency in agranulocytosis patients compared with control (23% versus 7%, P=0.03), as was ABCB1 (ABC-transporter-B1; drug efflux transporter) 3435TT (32% versus 20%, P=0.05). In patients developing neutropenia, ABCB1 3435TT and homozygosity for GSTT1[sup.null] (glutathione-S-transferase; conjugates reactive clozapine metabolites into glutathione) were more frequent compared with control (34% versus 20%, P=0.05 and 31% versus 14%, P=0.03), whereas GSTM1[sup.null] was less frequent in these patients (31% versus 52%, P=0.03). 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| ispartof | The Pharmacogenomics Journal, 2017, Vol.17 (5), p.471 |
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| language | eng |
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| source | Alma/SFX Local Collection |
| subjects | Clozapine Complications and side effects Drug metabolism Genetic aspects Genotypes Health aspects Neutropenia Risk factors |
| title | Genetic risk factors for clozapine-induced neutropenia and agranulocytosis in a Dutch psychiatric population |
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