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

PRISCILA AYELÉN PAGNOTTA; VIVIANA ALICIA MELITO ; JIMENA VERÓNICA LAVANDERA; VICTORIA ESTELA PARERA ; MARÍA VICTORIA ROSSETTI; JOHANNA ROMINA ZUCCOLI; ANA MARÍA BUZALEH

Biomedical Reports

Spandidos Publications

Año: 2020

2049-9434

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 ABCB1 gene variantsc.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. 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 ABCB1 and GSTP1 variants, and multiplex PCR was used to study the GSTM1 and GSTT1 variants. The high frequency of c.3435C>T (PCT andPCT-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 GSTT1 null and low frequency for GSTM1 null variants; thus, the genetic basis for PCT onset may 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 may influence the PCT‐HIV association. The present study is the first to investigate the possible role of GST and ABCB1 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 betweenPCT and HIV.