MDR1 gene polymorphisms in the association of Porphyria Cutanea Tarda and Human Immunodeficiency Virus IN Argentina

MELITO, VIVIANA; PARERA VICTORIA; ROSSETTI, MARIA VICTORIA; BATLLE, ALCIRA; LAVANDERA, JIMENA; BUZALEH, ANA MARIA

Lucerna

Congreso; INTERNATIONAL CONGRESS ON PORPHYRINS AND PORPHYRIAS; 2013

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.