CYP2D6 Genotype in Relation to Liver Toxicity Due to Tetrabenazine in Iraqi Patients with Hyperkinetic Movement Disorders

Abstract

Abstract The common types of movement disorders are ; dystonia which is a syndrome of repetitive muscle contractions. While , Huntington disease is autosomal dominant progressive neurodegenerative disorder, which is characterized by involuntary movements (“chorea”). Tetrabenazine therapy has been shown to effectively control this movements compared with placebo. Design the proper dosing approach for patients treated with tetrabenazine with genotype polymorphisms and their hepatic effect on patients. A prospective case controlled study was carried on 50 patients whom divided into 2 groups :first group involved 25 patients who had chorea, and group 2 included patients with dystonia, whom treated with (tetrabenazine) for three months. In addition to control group involved 25 healthy subjects . Blood samples were collected at the beginning and after three months to assess liver function in relation to genetic polymorphism of CYP 450 2D6 enzyme for both groups and measuring the plasma concentration of tetrabenazine , alpha and beta dyhdrotetrabenazine. The results show a significant CYP 450 2D6 enzyme polymorphism. And elevations of liver enzymes in the patient indicate hepatotoxicity of tetrabenazine and its metabolites, Determination a genotype of the CYP 450 2D6 genes in Iraqi patients, in relation to the safety and efficacy of tetrabenazine .

Keywords

• Dystonia, chorea, Tetraberazine, Alpha and Beta dihydrotetrabenazine, CYP 450 2D6 enzyme polymorphism, liver function.