CYP2D6 polymorphisms in patients with porphyrias

LAVANDERA, JIMENA; PARERA, VICTORIA; BATLLE, ALCIRA; BUZALEH, ANA MARIA

MOLECULAR MEDICINE

The Feinstein Institute for Medical Research

Lugar: NUEVA YORK, ESTADOS UNIDOS; Año: 2006 vol. 12 p. 259 - 263

1076-1551

        CYP2D6 polymorphisms result in poor (PM), intermediate (IM), ultrarrapid (UM), efficient (EM) and efficient intermediate metabolizers (EIM).        Porphyrias are inherited or acquired disorders of heme metabolism. Some of CYP2D6 substrate drugs are unsafe for porphyric patients. CYP2D6 polymorphisms presence in these individuals would be of influence in the triggering of the disease when they receive a precipitating agent that is metabolized by CYP2D6.        So, the aim of this work was to investigate CYP2D6 polymorphisms in porphyric patients.        The frequency of CYP2D6*3 and CYP2D6*4 alleles has been evaluated in 51 unrelated healthy Argentinean volunteers and in 50 individuals with Porphyria Cutanea Tarda (PCT) (15), Acute Intermittent Porphyria (AIP) (20) and Variegate Porphyria (VP) (15). Alleles were detected using the polymerase chain reaction (PCR) and the restriction fragment length polymorphism (RFLP).        Results indicated that 39% of control group showed EIM phenotype (20/51); 17 of them carrying the CYP2D6*4 allele and 3 of them carrying the CYP2D6*3 allele; 3.9% were PM (2/51), one of these subjects carried the CYP2D6*4 allele and the other one CYP2D6*3 allele.Among the porphyric population studied, 2/20 AIP, 4/15 PCT and 4/15 VP showed EIM phenotype. The frequency of EIM phenotype in AIP was lower than in healthy controls. In AIP and PCT subjects, only the CYP2D6*4 allele was found; while one individual of the VP group carried the CYP2D6*3 allele; 6.6% (1/15) PCT and VP were PM to CYP2D6*4 allele.        Frequencies of both alleles in Argentinean controls were similar to those of other Caucasian populations.