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

PAGNOTTA, PRISCILA; PARERA, VICTORIA; MELITO, VIVIANA; ZUCCOLI, JOHANNA; ROSSETTI MARÍA VICTORIA; BUZALEH, ANA MARIA; MANRIQUE BOJORQUEZ , NANCIBEL; BATLLE, ALCIRA

Mar del Plata

Congreso; Reunion Conjunta de Biociencias; 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 AIP onset. Glutathione-S-transferases (GST) are Phase II enzymes involved in detoxification of reactive oxygen species, environmental carcinogens, metabolism of steroid hormones and chemotherapeutic agents. Some polymorphisms in this gene, GSTT1 null, GSTM1 null and GSTP1 (rs1695, c.313 A>G), alter GST 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 moment of the diagnosis were symptomatics (S-AIP) or without clinical/biochemical alterations (latent group, L-AIP). GSTT1 and GSTM1 were amplified by multiplex PCR; GSTP1 variant by PCR-RFLP. The deletion frequencies in homozygosis for GSTT1 null were: 8.3 (control), 20.5 (S-AIP) and 6.1 % (L-AIP). Frequencies for GSTM1 null were: 41.7 (control), 51.3 (S-AIP) and 45.5 % (L-AIP). In S-AIP, null GSTT1 frequency was significantly high respect to control (p