Implications of MDR1 Polymorphisms in the Development of Porphyria Cutanea Tarda in HIV Infected Individuals

PAGNOTTA, PRISCILA; ROSSETTI, MARIA VICTORIA; MELITO, VIVIANA; LAVANDERA, JIMENA; BATLLE, ALCIRA; ZUCCOLI, JOHANNA; PARERA, VICTORIA; BUZALEH, ANA MARÍA

Burdeos

Congreso; ICPP Porphyrins and Porphyrias 2017; 2017

In Argentina, a high association of Porphyria Cutanea Tarda (PCT) with HIV infection is found (17%), however to date, slight evidence exists about if triggering factors of PCT in HIV patients are related to the infection and/or therapy. The multidrug resistance protein (MDR1) is involved in the transport of xenobiotics and antiretroviral drugs. A number of polymorphisms in MDR1 gene were found to be of clinical importance, among them: exon 12 (c.1236C>T), 21 (c.2677G>T/A) and 26 (c.3435C>T) with high incidence in Caucasians. The frequency of these SNPs was previously studied in control, PCT and PCT-HIV individuals. The aim was to complete this research analysing also HIV patients without PCT by PCR-RFLP assay. The analysis of 1236T-2677T/A-3435T haplotypes was performed using SNPStats program. The polymorphic allelic frequencies were 0.46 (exon 26), 0.33 (exon 12) and 0.43 (exon 21). Genotypic frequencies were as follows: exon 26: CC 23.1%, CT: 61.5%, TT 15.4%; exon 12: CC 33.3%, CT 66.7%, TT 0%; exon 21: GG 32.3%, GT 47.6%, TT 19.1%. In HIV population, the frequency of T allele for exon 26 was significant higher than control, but comparable to PCT and PCT-VIH groups. For exon 21, significant differences of T allele frequency was observed for PCT-HIV respect to the other groups; while for exon 12, the mutant allele was only different in PCT cohort. In conclusion, the polymorphism of exon 21 could be involved in the manifestation of PCT in HIV individuals related to the antiretroviral therapy used in these patients, while in exon 12, T allele could be associated with another risk factors.