Role of ABCB1 and Glutathione S-transferases genes variants in the association of Porphyria Cutanea Tarda and Human Immunodeficiency Virus infection

PAGNOTTA P; MELITO, VA; LAVANDERA, J; PARERA, VE; ROSSETTI, M.V; ZUCCOLI J; ZUCCOLI J; BUZALEH, AM

Biomedical Reports

Spandidos Publications

Lugar: Londres/Atenas; Año: 2020 vol. 13

2049-9434

In Argentina, Porphyria Cutanea Tarda (PCT) is highly associated with HumanImmunodeficiency Virus (HIV)infection, but it is not known whether or not the onset of thisdisease is related to HIV infection and/or the antiretroviral therapy. The ABCB1 gene variantsc.1236C>T, c.2677G>T/A and c.3435C>T affect drug efflux. The GSTT1 null, GSTM1 nulland GSTP1 (c.313A>G) gene variants alter Glutathione S-transferase (GST) activity,modifying the levels of xenobiotics. This study aimed to evaluate the role of genetic variantsin the triggering of PCT and to analyze the genetic basis of the PCT-HIV association. Controlindividuals and HIV, PCT and PCT-HIV patients were studied. PCR-RFLP was used togenotype the ABCB1 and GSTP1 variants, whereas multiplex PCR was used to study theGSTM1 and GSTT1 variants. The high frequencies of c.3435C>T (PCT and PCT-HIV) andc.1236C>T (PCT) suggest that the onset of PCT would not be related specifically to HIVinfection or antiretroviral therapy for these variants. c.2677G>T/A frequencies in PCT-HIVpatients were high, indicating that a mechanism involving antiretroviral therapy would play arole in this association. PCT-HIV patients also presented high frequency for GSTT1 null andlow frequency for GSTM1 null; thus, the genetic basis for PCT onset would involve acombination between the absence of GSTT1 and the presence of GSTM1. In conclusion, genesencoding for proteins involved in the flow and metabolism of xenobiotics would influence thePCT-HIV association. This is the first study that investigated the possible role of GST andABCB1 gene variants in the triggering of PCT in HIV-infected individuals, leading to newinsights into the molecular basis of the PCT-HIV association.