NEW RESULTS ABOUT THE RELATIONSHIP BETWEEN CYP2C9 SNPS AND ACUTE INTERMITTENT PORPHYRIA MANIFESTATION

GABRIELA NORA CERBINO; VICTORIA E PARERA; ABOU ASSALI LUBNA ; LAURA SABINA VARELA; MARÍA VICTORIA ROSSETTI; DIEGO MIGUEL GORDILLO; ALCIRA M DEL C. BATLLE

Mar del Plata

Congreso; LXIII Reunión Científica de la Sociedad Argentina de Investigacion Clinica (SAIC); 2018

SAIC

Alterations produced by polymorphisms would contribute to cause illness. So, the identification of variants in specific sequences of some gene is of very clinic importance. Porphyrias are a group of metabolic hereditary pathologies in which only the presence of the mutation in the gene codifying the deficient enzyme is not sufficient for porphyria manifestation. Stress, low calories intake and many porphyrinogenic drugs are known as triggering factors. So, genetic variants in xenobiotic metabolization enzymes have an essential role in symptomatology manifestation. It was suggested that SNPs in CYP2C9, that affect its activity, would play a role in Acute Intermittent Porphyria (AIP), the most frequent acute porphyria in our population. With the aim of verify this hypothesis we continued with the analysis of some reported SNPs in different exons: CYP2C9*3 (exon 7), CYP2C9*7 (exon 1) CYP2C9*6, CYP2C9*9 and CYP2C9*10 (exon 5) in a control population and in a group of AIP patients biochemically and genetically diagnosed at CIPYP. We started this study with the analysis of CYP2C9*3 in 30 healthy volunteers and 40 AIP patients, 11 symptomatic and 29 asymptomatic, and also the other SNPs mentioned above, in 10 samples selected from the same group of AIP. Molecular typing was performed by PCR and automatic sequencing. Considering the total population (70) the frequencies found for A/A and A/C genotypes were 0.95 and 0.05 respectively while C/C genotype was not present in Argentinean population. Surprisingly CYP2C9*3 was not present in AIP patient and neither SNPs in both exons 1 and 5, but we found others reported SNPs in introns 1, 6 and 7 which have no effect on the enzyme activity. According to our results, these genomic variants are not present in our population. We will continue analysing other regions of this CYP as well as SNPs described for CYP2C19.