Evaluation of The ABCB1 Genotype and Risks Factors in Dogs Affected By Refractory Idiopathic Epilepsy

Gagliardo, Teresa (2017) Evaluation of The ABCB1 Genotype and Risks Factors in Dogs Affected By Refractory Idiopathic Epilepsy, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Scienze veterinarie, 28 Ciclo. DOI 10.6092/unibo/amsdottorato/8145.
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Abstract

Despite the advances in the treatment of Idiopathic Epilepsy, still a relevant percentage of dogs don’t achieve an adequate seizure control despite the association of different anti-epileptic drugs (AEDs) at appropriate dosage. This condition, know as Refractory Epilepsy, is considered one of the most frustrating condition for pets, owners and neurologists. In human and veterinary medicine, great effort is spent in trying to elucidate the mechanisms underlying responsiveness and refractoriness to AEDs treatment. Recently, attention has been focused on the attempt to identify risk factors to predict the outcome of the disease and to understand the exact pathophysiological mechanisms of RIE. A key role seems to have P-glycoprotein encoded by the ABCB1 gene. It has been supposed that an over-expression of these efflux transporters, due to an ABCB1 mutation, may inhibit AED penetration in epileptic foci resulting in a reduced efficacy of antiepileptic treatment. A similar mechanism was hypothesized also in veterinary medicine, indeed a single nucleotide variation (SNV) of ABCB1 gene (c.-6- 180T>G) has been associated with phenobarbital-resistance in a population of idiopathic epileptic Border collie. In the present study, data from a population of Refractory Idiopathic Epileptic dogs (RIE-dogs) were statistically compared with a control group of AED-responsive dogs to identify clinical risk factors associated with RIE and the frequency of the ABCB1 c.-6-180T>G SNV were assessed in this multi-breed population affected by RIE. The present study confirmed that clinical risk factors for RIE include the early onset of seizures and the experience of cluster seizure and identified a higher risk to develop RIE in the Cane Corso and in the Border Collie breed. Furthermore, the study confirmed the presence of the c.-6-180T>G polymorphism in several breeds and failed to identify any association with RIE.

Abstract
Tipologia del documento
Tesi di dottorato
Autore
Gagliardo, Teresa
Supervisore
Dottorato di ricerca
Scuola di dottorato
Scienze veterinarie
Ciclo
28
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
Refractory idiopathic epilepsy, P-glycoprotein, ABCB1
URN:NBN
DOI
10.6092/unibo/amsdottorato/8145
Data di discussione
21 Aprile 2017
URI

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