Studies of the role of CYP2C9 SNPs on Acute Intermittent Porphyria manifestation.

LUBNA ABOU ASSALI; DIEGO MIGUEL GORDILLO; GABRIELA NORA CERBINO; LAURA SABINA VARELA; ALCIRA MARÍA DEL CARMEN BATLLE; VICTORIA ESTELA PARERA; MARÍA VICTORIA ROSSETTI

Buenos Aires

Otro; LXII Reunión Anual la Sociedad Argentina de Investigación Clínica (SAIC); 2017

SOCIEDAD ARGENTINA DE INVESTIGACION CLINICA

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. Many porphyrinogenic drugs as barbiturates, anaesthetics, anti-inflammatories, antibiotics, anticonvulsants and others are known as triggering factors. So, genetic variants in xenobiotics metabolization enzymes have an essential role in symptomatology manifestation. It was suggested that SNPs in CYP2C9, that affect its activity and/ or expression, would play a role in the manifestation of the most frequent acute porphyria in our population, Acute Intermittent Porphyria (AIP). With this aim, we started the first analysis in world literature studying the presence of allele CYP2C9*2 (rs: 1799853), which diminished its enzyme activity, in both, a control population and AIP patients diagnosed at CIPYP. We selected samples of 50 individuals, 13 healthy volunteers and 37 AIP patients, 18 symptomatic and 19 asymptomatic. Molecular typing was performed by PCR and automatic sequencing. The Fisher exact test was used to detect differences in alleles and genotype frequencies, odds ratio and 95% confidential interval. Considering the total population (50) the frequencies found for C/C and C/T genotypes were 0.72 and 0.20 respectively while genotype T/T was not present in Argentinean population. There is no significant difference between genotype and allelic frequencies comparing control and AIP patients. When we compared these parameters between the group of symptomatic and asymptomatic AIP patients no significant difference was found; p= 0.195, OR=2.6 and IC (95%) = 0.55-12 for genotype variants and p= 0.2130, OR=2.33 and IC (95%)=0.53-10 respectively. According these results, CYP2C9*2 allele do not have any role in AIP manifestation. We are following this study increasing the number of individuals and also searching other variants in this CYP. Keywords: porphyrias, acute intermittent porphyria, CYP2C9