The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
NAD(P)H Oxidase and Multidrug Resistance Protein Genetic Polymorphisms Are Associated With Doxorubicin-Induced Cardiotoxicity
Abstract
Background—A significant number of patients treated with anthracyclines develop cardiotoxicity (anthracycline-induced cardiotoxicity [ACT]), mainly presenting as arrhythmias (acute ACT) or congestive heart failure (chronic ACT). There are no data on pharmacogenomic predictors of ACT. Methods and Results—We genotyped participants of the German non-Hodgkin lymphoma study (NHL-B) who were followed up for the development of heart failure for a median of >3 years. Single-nucleotide polymorphisms (SNPs) were selected from 82 genes with conceivable relevance to ACT. Of 1697 patients, 55 developed acute and 54 developed chronic ACT (cumulative incidence of either form, 3.2%). We detected 5 significant associations with polymorphisms of the NAD(P)H oxidase and doxorubicin efflux transporters. Chronic ACT was associated with a variant of the NAD(P)H oxidase subunit NCF4 (rs1883112, −212A→G; symbols with right-pointing arrows, as edited?‘ odds ratio [OR], 2.5; 95% CI, 1.3 to 5.0). Acute ACT was associated with the His72Tyr polymorphism in the p22phox subunit (rs4673; OR, 2.0; 95% CI, 1.0 to 3.9) and with the variant 7508T→A (rs13058338; OR, 2.6; 95% CI, 1.3 to 5.1) of the RAC2 subunit of the same enzyme. In agreement with these results, mice deficient in NAD(P)H oxidase activity, unlike wild-type mice, were resistant to chronic doxorubicin treatment. In addition, acute ACT was associated with the Gly671Val variant of the doxorubicin efflux transporter multidrug resistance protein 1 (MRP1) (OR, 3.6; 95% CI, 1.6 to 8.4) and with the Val1188Glu-Cys1515Tyr (rs8187694-rs8187710) haplotype of the functionally similar MRP2 (OR, 2.3; 95% CI, 1.0 to 5.4). Polymorphisms in adrenergic receptors previously demonstrated to be predictive of heart failure were not associated with ACT. Conclusions—Genetic variants in doxorubicin transport and free radical metabolism may modulate the individual risk to develop ACT.
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Cites
Overexpression of a Transporter Gene in a Multidrug-Resistant Human Lung Cancer Cell Line
Cole, S. P. C., Bhardwaj, G., Gerlach, J. H., Mackie, J. E., Grant, C. E., Almquist, K. C., Stewart, A. J., Kurz, E. U., Duncan, A. M. V., & Deeley, R. G. (1992) · Science · doi:10.1126/science.1360704 · Cited by 3,037
Pollock, J. D., Williams, D. A., Gifford, M. A. C., Li, L. L., Du, X., Fisherman, J., Orkin, S. H., Doerschuk, C. M., & Dinauer, M. C. (1995) · Nature Genetics · doi:10.1038/ng0295-202 · Cited by 921
Cited by
Doxorubicin pathways: pharmacodynamics and adverse effects
Thorn, C. F., Oshiro, C., Marsh, S., Hernandez-Boussard, T., McLeod, H., Klein, T. E., & Altman, R. B. (2011) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e32833ffb56 · Cited by 1,648
Rawat, P. S., Jaiswal, A., Khurana, A., Bhatti, J. S., & Navik, U. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111708 · Cited by 909
Anthracycline Cardiotoxicity: Prevalence, Pathogenesis and Treatment
Volkova, M., & Russell, R. (2012) · Current Cardiology Reviews · doi:10.2174/157340311799960645 · Cited by 872
Pharmacogenomic Prediction of Anthracycline-Induced Cardiotoxicity in Children
Visscher, H., Ross, C. J. D., Rassekh, S. R., Barhdadi, A., Dubé, M.-P., Al-Saloos, H., Sandor, G. S., Caron, H. N., van Dalen, E. C., Kremer, L. C., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2010.34.3467 · Cited by 401
Pharmacogenomics of Drug Metabolizing Enzymes and Transporters: Relevance to Precision Medicine
Ahmed, S., Zhou, Z., Zhou, J., & Chen, S.-Q. (2016) · Genomics, Proteomics & Bioinformatics · doi:10.1016/j.gpb.2016.03.008 · Cited by 371
Metadata
- Authors
- Wojnowski, L., Kulle, B., Schirmer, M., Schlüter, G., Schmidt, A., Rosenberger, A., Vonhof, S., Bickeböller, H., Toliat, M. R., Suk, E.-K., Tzvetkov, M., Kruger, A., Seifert, S., Kloess, M., Hahn, H., Loeffler, M., Nürnberg, P., Pfreundschuh, M., Trümper, L., Brockmöller, J., & Hasenfuss, G.
- Venue
- Circulation
- Published
- 2005-12-13
- Volume
- 112
- Issue
- 24
- Pages
- 3754-3762
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2116678763
- Cited by
- 489
- References
- 2
- FWCI
- 9.33
- Type
- journal article
- Language
- en
- Open access
- closed
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- Wojnowski, L., Kulle, B., Schirmer, M., Schlüter, G., Schmidt, A., Rosenberger, A., Vonhof, S., Bickeböller, H., Toliat, M. R., Suk, E.-K., Tzvetkov, M., Kruger, A., Seifert, S., Kloess, M., Hahn, H., Loeffler, M., Nürnberg, P., Pfreundschuh, M., Trümper, L., . . . Hasenfuss, G. (2005). NAD(P)H Oxidase and Multidrug Resistance Protein Genetic Polymorphisms Are Associated With Doxorubicin-Induced Cardiotoxicity. Circulation. https://doi.org/10.1161/circulationaha.105.576850
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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