MDR1 POLYMORPHIMS AND ACUTE INTERMITTENT PORPHYRIA

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

Milan

Congreso; INTERNATIONAL CONGRESS ON PORPHYRIAS AND PORPHYRINS; 2019

ICCP

Acute Intermittent Porphyria (AIP), a metabolic disease caused by an inherited deficiency of Porphobilinogen deaminase (PBG-D. The reduction of enzyme activity is not enough for the triggering of these symptoms and crisis may be precipitated by several factors, including therapeutic drugs. Thus drug metabolic system and transport could play a role in AIP onset. More than 50 polymorphisms in the multidrug resistance (MDR1) gene, that codes for drug transport P-gp protein, are of clinical importance affecting drug transport an availability, among them: exon 12 (c.1236C>T), 21 (c.2677G>T/A) and 26 (c.3435C>T) with high incidence in Caucasians. Several P-gp substrates are unsafe drugs for AIP patients. The aim was to evaluate the role of MDR1 in AIP triggering. Studied population: Control (N=60, no AIP), AIP-S (n=35) with clinical symptoms, biochemical characteristic alterations and the mutation in PBG-D gene and AIP-L (N=31) only carrying the mutation in PBG-D gene. Exons 26, 12 and 21 were genotyped by PCR-RFLP; haplotypes were performed with SNPStats program. The polymorphic T allele frequency was significantly elevated (p