التفاصيل البيبلوغرافية
| العنوان: |
NAD(P)H oxidase and multidrug resistance protein genetic polymorphisms are associated with doxorubicin-induced cardiotoxicity |
| المؤلفون: |
Wojnowski, L., Kulle, B., Schirmer, M., Schlüter, G., Schmidt, A., Rosenberger, A., Vonhof, S., Bickeböller, H., Toliat, M., Suk, E., Tzvetkov, M., Kruger, A., Seifert, S., Kloess, M., Hahn, H., Loeffler, M., Nürnberg, P., Pfreundschuh, M., Trümper, L., Brockmöller, J., Hasenfuss, G. |
| المصدر: |
Circulation |
| سنة النشر: |
2005 |
| المجموعة: |
Max Planck Society: MPG.PuRe |
| الوصف: |
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. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| العلاقة: |
http://hdl.handle.net/11858/00-001M-0000-0010-8558-1Test |
| الإتاحة: |
http://hdl.handle.net/11858/00-001M-0000-0010-8558-1Test |
| رقم الانضمام: |
edsbas.902D5922 |
| قاعدة البيانات: |
BASE |
