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

PAGNOTTA, PRISCILA; MELITO, VIVIANA; LAVANDERA JIMENA; PARERA, VICTORIA; ROSSETTI, MARIA VICTORIA; ZUCCOLI, JOHANNA; BUZALEH ANA MARIA (CORRESPONDING AUTHOR)

Biomedical Reports

Spandidos

Año: 2020

2049-9434

In Argentina, Porphyria Cutanea Tarda (PCT) is highly associated with Human Immunodeficiency Virus (HIV)infection, but it is not known whether or not the onset of this disease is related to HIV infection and/or the antiretroviral therapy. The ABCB1 gene variants c.1236C>T, c.2677G>T/A and c.3435C>T affect drug efflux. The GSTT1 null, GSTM1 null and 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 variants in the triggering of PCT and to analyze the genetic basis of the PCT-HIV association. Control individuals and HIV, PCT and PCT-HIV patients were studied. PCR-RFLP was used to genotype the ABCB1 and GSTP1 variants, whereas multiplex PCR was used to study the GSTM1 and GSTT1 variants. The high frequencies of c.3435C>T (PCT and PCT-HIV) and c.1236C>T (PCT) suggest that the onset of PCT would not be related specifically to HIV infection or antiretroviral therapy for these variants. c.2677G>T/A frequencies in PCT-HIV patients were high, indicating that a mechanism involving antiretroviral therapy would play a role in this association. PCT-HIV patients also presented high frequency for GSTT1 null and low frequency for GSTM1 null; thus, the genetic basis for PCT onset would involve a combination between the absence of GSTT1 and the presence of GSTM1. In conclusion, genes encoding for proteins involved in the flow and metabolism of xenobiotics would influence the PCT-HIV association. This is the first study that investigated the possible role of GST and ABCB1 gene variants in the triggering of PCT in HIV-infected individuals, leading to new insights into the molecular basis of the PCT-HIV association.