Polymorphisms of CYP2D6 in control and porphyric individuals: Frequency of Ultrarapid Metabolizers

LAVANDERA, JIMENA; PARERA, VICTORIA; ROSSETTI, MARIA VICTORIA; MC KEON, SOLEDAD; BATLLE ALCIRA; BUZALEH, ANA MARIA

Nucleotide Substitution

Academy Publish

Año: 2012;

The porphyrias are diseases resulting from genetically partial deficiencies in one of the heme biosynthetic enzymes. From their clinical manifestations they can be classified into cutaneous, acute and mixed disorders. Porphyria Cutanea Tarda (PCT), is the most common of cutaneous porphyrias, in which the activity of uroporphyrinogen decarboxylase is reduced approximately 50%. Acute Intermitent Porphyria (AIP) is the most common of acute porphyrias due to a 50% deficiency in the activity of porphobilinogen deaminase. Triggering of clinical signs is produced by exposure to exogenous precipitating factors, including commonly prescribed drugs. CYP2D6 polymorphisms cause inter-individual variability in drug response. Five phenotypes can be distinguished: poor (PM), intermediate (IM), ultrarapid (UM), efficient (EM) and efficient intermediate metabolizers (EIM). Some of CYP2D6 substrate drugs are unsafe for porphyric patients. Here, we reviewed our previous and present research on the identification of polymorphisms of CYP2D6 in control and porpyric individuals with the aim of searching if there is any association between these polymorphisms and the onset of the disease. The identification of CYP2D6 UM frequency in porphyric patients and in a control group is described in extent. In the control population analyzed, 13% presented CYP2D6 gene duplicated. In the porphyric group, this frequency was lower although the difference was not significant between PCT (5.3%) and AIP (4.5%) and control group. Predictive genotyping for CYP2D6 in porphyric patients could be used routinely to personalize drug administration, due to the fact that in these patients some drugs have shown conflictive evidence about their porphyrinogenicity.