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Abstract:

The cytochrome P-450 (CYP) isoenzymes, a superfamily of heme proteins which are the terminal oxidases of the mixed function oxidases system, metabolize more than 70% of all clinically approved drugs. The highly polymorphic CYP2D6 isoform metabolizes more than 25% of most common drugs, and the phenotypes of the 70-plus allelic variants range from compromised to excessive enzymatic activity. Porphyrias are a group of inherited or acquired metabolic disorders of heme biosynthesis, due to a specific decrease in the activity of one of the enzymes of the heme pathway. Clinical signs and symptoms of porphyrias are frequently associated with exposure to precipitating agents, including clinically approved drugs. CYP enzymes, including CYP2D6, participate in the metabolism of some porphyrinogenic drugs, leading to the deregulation of heme biosynthesis. Considering that some of the drugs not recommended for use in porphyric patients are metabolized by CYP2D6, the presence of CYP2D6 polymorphisms in porphyric patients would influence the triggering of the disease when these individuals receive a precipitating agent that is metabolized by CYP2D6. To investigate CYP2D6 polymorphisms in porphyric patients, healthy Argentinean volunteers, porphyric patients, and a group of individuals with high levels of iron were studied. Results indicated that the CYP2D6*3 and CYP2D6*4 alleles, in particular, would be linked to the onset of disease. Predictive genotyping for CYP2D6 in porphyric patients holds promise as a method to improve the clinical efficacy of drug therapy and to personalize drug administration for these patients.

Registro:

Documento: Artículo
Título:CYP2D6 polymorphisms in patients with porphyrias
Autor:Lavandera, J.V.; Parera, V.E.; Batlle, A.; Buzaleh, A.M.
Filiación:Centro de Investigaciones Sobre Porfirinas y Porfirias (CIPYP), CONICET, Hospital de Clínicas, Argentina
Department of Biological Chemistry, Facultad de Ciencias Exactas y Naturales, University of Buenos Aires, Argentina
Viamonte 1881 10 A, C1056ABA, Buenos Aires, Argentina
Palabras clave:cytochrome P450 2D6; hemoprotein; iron; isoenzyme; oxidoreductase; porphyrin derivative; adult; aged; allele; Argentina; article; clinical feature; controlled study; cytochrome P2D6 gene; disease association; DNA polymorphism; drug exposure; drug metabolism; enzyme activity; enzyme metabolism; enzyme regulation; female; gene; genetic analysis; genotype phenotype correlation; heme synthesis; human; iron blood level; major clinical study; male; metabolic disorder; porphyria; priority journal; protein family; protein function; Adolescent; Adult; Alleles; Child; Cytochrome P-450 CYP2D6; Female; Gene Frequency; Genotype; Humans; Male; Middle Aged; Phenotype; Polymorphism, Genetic; Porphyrias
Año:2006
Volumen:12
Número:9-10
Página de inicio:259
Página de fin:263
DOI: http://dx.doi.org/10.2119/2005-00047.Lavandera
Título revista:Molecular Medicine
Título revista abreviado:Mol. Med.
ISSN:10761551
CODEN:MOMEE
CAS:iron, 14093-02-8, 53858-86-9, 7439-89-6; oxidoreductase, 9035-73-8, 9035-82-9, 9037-80-3, 9055-15-6; Cytochrome P-450 CYP2D6, EC 1.14.14.1
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10761551_v12_n9-10_p259_Lavandera

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Citas:

---------- APA ----------
Lavandera, J.V., Parera, V.E., Batlle, A. & Buzaleh, A.M. (2006) . CYP2D6 polymorphisms in patients with porphyrias. Molecular Medicine, 12(9-10), 259-263.
http://dx.doi.org/10.2119/2005-00047.Lavandera
---------- CHICAGO ----------
Lavandera, J.V., Parera, V.E., Batlle, A., Buzaleh, A.M. "CYP2D6 polymorphisms in patients with porphyrias" . Molecular Medicine 12, no. 9-10 (2006) : 259-263.
http://dx.doi.org/10.2119/2005-00047.Lavandera
---------- MLA ----------
Lavandera, J.V., Parera, V.E., Batlle, A., Buzaleh, A.M. "CYP2D6 polymorphisms in patients with porphyrias" . Molecular Medicine, vol. 12, no. 9-10, 2006, pp. 259-263.
http://dx.doi.org/10.2119/2005-00047.Lavandera
---------- VANCOUVER ----------
Lavandera, J.V., Parera, V.E., Batlle, A., Buzaleh, A.M. CYP2D6 polymorphisms in patients with porphyrias. Mol. Med. 2006;12(9-10):259-263.
http://dx.doi.org/10.2119/2005-00047.Lavandera