Role of ABCB1 and glutathione S-transferase gene variants in the association of porphyria cutanea tarda and human immunodeficiency virus infection

In Argentina, porphyria cutanea tarda (PCT) is strongly associated with infection with human immunodeficiency virus (HIV); however, whether the onset of this disease is associated with HIV infection and/or the antiretroviral therapy has not been determined. The gene variants c.1236C>T, c.2677G>T/A and c.3435C>T affect drug efflux. The null, null and (c.313A>G) gene variants alter Glutathione S-transferase (GST) activity, modifying the levels of xenobiotics. The aim of the present study was to evaluate the role of genetic variants in initiation of PCT and to analyze the genetic basis of the PCT-HIV association. Control individuals, and HIV, PCT and PCT-HIV patients were recruited, PCR-restriction fragment length polymorphism was used to genotype the and variants, and multiplex PCR was used to study the and variants. The high frequency of c.3435C>T (PCT and PCT-HIV) and c.1236C>T (PCT) suggested that the onset of PCT were not specifically related to HIV infection or antiretroviral therapy for these variants. c.2677G>T/A frequencies in the PCT-HIV patients were higher compared with the other groups, suggesting that a mechanism involving antiretroviral therapy served a role in this association. PCT-HIV patients also had a high frequency of null and low frequency for null variants; thus, the genetic basis for PCT onset may involve a combination between the absence of and the presence of . In conclusion, genes encoding for proteins involved in the flow and metabolism of xenobiotics may influence the PCT-HIV association. The present study is the first to investigate the possible role of and gene variants in the triggering of PCT in HIV-infected individuals, to the best of our knowledge, and may provide novel insights into the molecular basis of the association between PCT and HIV.