INVESTIGADORES
BUZALEH Ana Maria
congresos y reuniones científicas
Título:
Porphyria Cutanea Tarda associated with human innmunodeficiency virus: identification of CY3A5 and CYP2B6 polymorphisms.
Autor/es:
LAVANDERA, JIMENA; MARTINEZ MARIA DEL CARMEN; PARERA, VICTORIA; ROSSETTI, MARIA VICTORIA; BATLLE, ALCIRA; BUZALEH, ANA MARIA
Lugar:
Cardiff
Reunión:
Congreso; International Porphyrins and Porphyrias Meeting; 2011
Institución organizadora:
British Journal of Dermatologists
Resumen:
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 0Æ89 in PCT-HIV group. CYP2B6*6 frequencies
were 0,31 in control group, 0,34 in PCT group and 0Æ30
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.