MDR1 polymorphims and Acute Intermittent Porphyria

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

Mar del Plata

Congreso; REUNION CONJUNTA DE SOCIEDADES BIOMEDICAS, LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

SAIC

Acute Intermittent Porphyria (AIP), a metabolic disease caused by an inherited deficiency of Porphobilinogen deaminase (PBG-D), is characterized by a neuroabdominal syndrome. 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. More than 50 polymorphisms in the multidrug resistance (MDR1) gene, that codes for drug transport P-gp protein, are of clinical importance, 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) and AIP (n=34) that had clinical symptoms, biochemical alterations characteristic of this disease and the mutation in PBG-D gene was detected. 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