Implication of glutathione S-transferases gene variants on Acute Intermittent Porphyria onset.

PAGNOTTA P; ZUCCOLI J; MANRIQUE BOJORQUEZ, N; PARERA, VE; ROSSETTI, MV; BATLLE, A; MELITO, VA; BUZALEH, AM

Mar del Plata

Congreso; REUNION CONJUNTA DE SOCIEDADES BIOMEDICAS, LXIV Reunión de la Sociedad Argentina de Investigación Clínica (SAIC); 2019

SAIC

Acute Intermittent Porphyria (AIP) is a result of a partial and primary deficiency in Porphobilinogen deaminase (PBG-D), the third enzyme in the heme pathway. The presence of the mutation is not enough for the manifestation of AIP which can be triggered by therapeutic drugs, so genetic variants in cell detoxification system could be involved in AIPonset. Glutathione-S-transferases (GST) are Phase II enzymesinvolved in detoxification of reactive oxygen species,environmental carcinogens, metabolism of steroid hormones andchemotherapeutic agents. Some polymorphisms in this gene,GSTT1 null, GSTM1 null and GSTP1 (rs1695, c.313 A>G), alterGST activity affecting hormones and xenobiotics levels. The aim was to analyze these variants in relation with AIP manifestation.The study was performed in control individuals (non porphyric)and in AIP patients carrying PBG-D mutation who at the momentof the diagnosis were symptomatics (S-AIP) or withoutclinical/biochemical alterations (latent group, L-AIP). GSTT1 andGSTM1 were amplified by multiplex PCR; GSTP1 variant by PCRRFLP. The deletion frequencies in homozygosis for GSTT1 nullwere: 8.3 (control), 20.5 (S-AIP) and 6.1 % (L-AIP). Frequenciesfor GSTM1 null were: 41.7 (control), 51.3 (S-AIP) and 45.5 %(L-AIP). In S-AIP, null GSTT1 frequency was significantly highrespect to control (p