PERSONAL DE APOYO
MELITO Viviana Alicia
congresos y reuniones científicas
Título:
MDR1 GENE POLYMORPHISMS IN THE ASSOCIATION OF PORPHYRIA CUTANEA TARDA AND HUMAN IMMUNODEFICIENCY VIRUS IN ARGENTINA
Autor/es:
MELITO, V; PARERA, V; ROSSETTI, M.V; BATLLE, A; LAVANDERA, J; BUZALEH, AM
Lugar:
Lucerna
Reunión:
Congreso; International Congress of Porphyrins and Porphyrias; 2013
Resumen:
Porphyria Cutanea Tarda (PCT) is the most common Porphyria in
Argentina, with a prevalence of about 1:25,000. Although, the clinical
manifestation of PCT is frequently associated with exposure to
precipitating agents such as hepatotoxic drugs and hepatothropic
virus infection, many biological variables could also be involved in
its triggering, like genetic polymorphisms of Phase I or Phase II drug
metabolism enzymes or transporters like the multidrug resistance
transporter gene (MDR1).
In Argentina, a high incidence (14.5 % ) of HIV infection in PCT
patients is found. Previously we evaluated the frequency of the polymorphisms
of CYP3A5 and CYP2B6, isoforms involved in the metabolization
of antiretroviral drugs, in a population of PCT and PCT/HIV
patients. No significant differences in the frequency of these CYP
polymorphisms were observed. MDR1 actively pumps out of the cell
xenobiotics such as antiretroviral drugs, protease inhibitors and
integrase inhibitors. A few single nucleotide polymorphisms (SNPs)
significantly affects expression of this protein and would alter drug
response.
The aim was to investigate if the incidence of MDR1 polymorphism
could influence the onset of PCT in subjects with HIV after
antiretroviral exposure. To this end, we have identified the MDR1
genotype C3435T (exon 26). A total of 105 subjects, 52 healthy volunteers,
26 PCT patients and 27 with PCT/HIV, were included in the
study, all of them of Caucasian origin. PCR-RFLP was performed to
evaluate the presence of polymorphisms.
The genotypic frequency observed was in healthy group:
CC = 34.6 % (18/52), CT = 61.5 % (32/52) and TT = 3.9 % (2/52); in PCT
patients: CC = 13.8 % (3/26), CT = 51.7 % (14/26) and TT = 34.5 % (9/26);
and in PCT/HIV: CC = 11.1 % (5/27), CT = 55.6 % (15/27) and TT = 33.3 %
(9/27). The allelic frequency was 0.35 (control), 0.62 (PCT) and
0.54 (PCT-VIH). A significant difference between healthy and PCT
(p < 0.001) or PCT-HIV (p < 0.05) groups was observed; while no statistical
difference was detected between the PCT and PCT/HIV groups.
In conclusion, the high prevalence of T allele in PCT individuals
found could be related to the onset of PCT independently of
HIV infection. To date, no data concerning MDR polymorphisms
have been reported in porphyric patients in Argentina. Further
investigations in this population, including the study of others
MDR1 genotypes such as C1236T (exon 12), should be performed to
evaluate the existence of a haplotype that could be related to PCT
manifestation.
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