PORPHYRIA CUTANEA TARDA ASSOCIATED TO HUMAN IMMUNODEFICIENCY VIRUS. IDENTIFICATION OF CYP3A5 AND CYP2B6 POLYMORPHISMS

LAVANDERA J; MARTINEZ M; PARERA VE; ROSSETTI MV; BATLLE A; BUZALEH, ANA MARIA

CARDIFF

Congreso; Porphyrins and Porphyrias 2011; 2011

British Association of Dermatologists

Porphyria cutanea tarda (PCT) is the most common of the porphyria disease, with a prevalence ranging from 1:5,000 to 1:25,000 people. 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 the human immunodeficiency virus (HIV). Data from Argentina reported a very high incidence of this association, showing 1:10 prevalence of HIV in PCT patients from this country. The metabolism of protease and reverse transcriptase inhibitors 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 its toxicity effects. 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, a few or no data concerning prevalence of polymorphisms in drug metabolism genes of antiretroviral drugs have been reported in the Argentinean population or in porphyric individuals worldwide. A total of 142 subjects, 60 healthy volunteers, 82 unrelated porphyric patients, were included in the study. The porphyric patient group, previously studied in our Centre, consisted of 82 individuals diagnosed as Porphyria Cutanea Tarda (PCT) from which, 22 were HIV positive. PCR-RFLP 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. 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 or 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 a different groups analyzed, there are an enormous number of 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 have more than one factor responsible for the onset of PCT symptoms.