Porphyria cutanea tarda associated with human immunodeficiency virus: identification of CYP3A5 and CYP2B6 polymorphisms

LAVANDERA, JIMENA; MARTÍNEZ, MARIA DEL CARMEN; PARERA, VICTORIA; ROSSETTI, MARÍA VICTORIA; BATLLE, ALCIRA; BUZALEH, ANA MARIA

Cardiff

Congreso; PORPHYRINS & PORPHYRIAS; 2011

British Association of Dermatologists

Porphyria cutanea tarda (PCT) is the most common of the porphyria diseases, with a prevalence ranging from 1: 5000 to 1: 25 000. In Argentina this prevalence is 1: 36 000. The clinical manifestation of PCT is frequently associated with exposure to precipitating agents and virus infection such as with human immunodeficiency virus (HIV). Data from Argentina reported a very high incidence of this association, showing a 1: 10 prevalence of HIV in PCT patients from this country. The metabolism of protease and reverse transcriptase inhibitor drugs used for HIV therapy differs due to CYP3A5 and CYP2B6 polymorphisms, respectively. Consequently, interindividual variation in the metabolism of CYP3A5 and CYP2B6 substrates is a factor in determining individual drug efficacy and also toxicity. The purpose of the current investigation was to determine whether interindividual differences in CYP3A5*3, CYP3A5*6 and CYP2B6*6 genotype could influence the trigger of PCT in subjects with HIV after antiretroviral exposure. To date, few or no data concerning prevalence of polymorphisms in drug metabolism genes of antiretroviral drugs have been reported in the Argentinian population or in porphyric individuals worldwide. In total, 142 subjects (60 healthy volunteers and 82 unrelated porphyric patients) were included in the study. The porphyric patient group, previously studied in our centre, consisted of 82 individuals diagnosed with PCT, of whom 22 were HIV positive. Polymerase chain reaction restriction fragment length polymorphism analysis was performed to evaluate the presence of polymorphisms. The frequencies of CYP3A5*3 were 0.91 in control group, 0.89 in PCT patients and 0.89 in PCT-HIV group. CYP2B6*6 frequencies were 0.31 in control group, 0.34 in PCT group and 0.30 in PCT-HIV group. We have shown that the allelic frequencies of CYP3A5*3 and CYP2B6*6 among our population were similar to those reported for other caucasian populations. Although we have not found significant differences in polymorphisms of CYP3A5 and CYP2B6 between the different groups analysed, there are many biological variables that may influence antiretroviral treatment, like other genetic polymorphisms, such as phase I or phase II drug metabolism enzymes, or transporters like multidrug resistance transporter gene (MDR1), which can contribute to drug toxicities and response or even it is possible that the PCT–HIV association may have more than one factor responsible for the onset of PCT symptoms.