Porphyrinogenicity of drugs in Acute Intermittent Porphyria: are the CYP-450 polymorphisms the answer?

VICTORIA TEMIÑO; GEREZ ESTHER; ROSSETTI, MARIA VICTORIA

Mar del Plata

Congreso; Sociedad Argentina de Investigación Clínica; 2019

Acute Intermittent Porphyria (AIP) is a hepatic pathology characterized by the accumulation of porphyrin precursors. It has sudden neurovisceral manifestations, commonly known as acute attacks or crises, which are triggered by exposure to different factors (fasting, stress, hormones and commonly used medications). Many hypotheses try to explain the variability in the prediction of the porphyrinogenicity of drugs, among which are the genetic polymorphisms of the CYP-450 enzymes. In this study, we wanted to verify if the difference in the triggering of an acute crisis was given by some of the most frequent and clinical significant polymorphisms of the enzymes of the CYP3A family, or even by a difference in their expression, given by the AKR1D1, an enzyme that regulates the expression of various CYPs and whose polymorphisms would augment CYPs expression. Peripheral blood samples of AIP patients (n=50) and no AIP patients were analyzed (n=74) by PCR-RFLP and PCR-sequencing. The variants analyzed were CYP3A4*22, CYP3A5*3, and AKR1D1 rs1872929 and rs1872930.Both allelic and genotypic frequencies found in the AIP group are very similar to those of the non-AIP group. So, when they were statistically analyzed with the X2 test (p