Bioinformatic complementation of the role of genetic variants in the manifestation of porphyrias

PAGNOTTA, PRISCILA; MELITO, VIVIANA; ZUCCOLI, JOHANNA; BUZALEH ANA MARIA; BUSCALIA, MARIA LAURA; PARERA, VICTORIA

Mar del Plata

Congreso; CONGRESO DE BIOCIENCIAS 2022; 2022

SAIC

Porphyrias are a group of metabolic diseases caused by failures in heme biosynthesis. Porphyria Cutanea Tardia (PCT), caused by a deficiency in the Uroporphyrinogen decarboxylase enzyme, is highly associated with HIV infection. The mutation in Porphobilinogen deaminase is not enough for the appearance of symptoms in Acute Intermittent Porphyria (AIP).Experimentally, we observed that symptomatic AIP and PCT-HIV individuals present a higher frequency of non-wild type variants of ABCB1 and Glutathion S-transferases (GSTs). The aim was to use databases to complement this study. Pubmed and Scielo (meta-analysis following the guidelines of PRISMA), 1000Genomes, PharmGKB, Gene Expression Omnibus (GEO, GSE44228), UniProt, Ensembl, and GenBank were used.The experimental results of the control group matched with the meta-analysis and with that reported in 1000Genomes. Gene frequencies varied between different regions of the planet.Some drugs for the treatment of HIV increase the probability of toxicity in individuals with experimentally tested variants: Efavirenz and Nelfinavir (rs1045642, ABCB1), Atazanavir (rs2032582, ABCB1) and Nevirapine (rs1045642, ABCB1; Presence, GSTM1).Using an array (GSE44228), individuals treated with protease inhibitors had lower expression of ABCB1 (FC=0.83, p adj