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Development of an oligonucleotide microarray for simultaneous detection of two canine MDR1 genotypes and association between genotypes and chemotherapy side effects
Journal of Veterinary Science ; : 27-33, 2019.
Artículo en Inglés | WPRIM | ID: wpr-758887
ABSTRACT
Canine MDR1 gene mutations produce translated P-glycoprotein, an active drug efflux transporter, resulting in dysfunction or over-expression. The 4-base deletion at exon 4 of MDR1 at nucleotide position 230 (nt230[del4]) in exon 4 makes P-glycoprotein lose function, leading to drug accumulation and toxicity. The G allele of the c.-6-180T>G variation in intron 1 of MDR1 (single nucleotide polymorphism [SNP] 180) causes P-glycoprotein over-expression, making epileptic dogs resistant to phenobarbital treatment. Both of these mutations are reported to be common in collies. This study develops a more efficient method to detect these two mutations simultaneously, and clarifies the genotype association with the side effects of chemotherapy. Genotype distribution in Taiwan was also investigated. An oligonucleotide microarray was successfully developed for the detection of both genotypes and was applied to clinical samples. No 4-base deletion mutant allele was detected in dogs in Taiwan. However, the G allele variation of SNP 180 was spread across all dog breeds, not only in collies. The chemotherapy adverse effect percentages of the SNP 180 T/T, T/G, and G/G genotypes were 16.7%, 6.3%, and 0%, respectively. This study describes an efficient way for MDR1 gene mutation detection, clarifying genotype distribution, and the association with chemotherapy.
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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Fenobarbital / Taiwán / Intrones / Exones / Miembro 1 de la Subfamilia B de Casetes de Unión a ATP / Análisis de Secuencia por Matrices de Oligonucleótidos / Quimioterapia / Alelos / Genotipo / Métodos Tipo de estudio: Estudio diagnóstico Límite: Animales País/Región como asunto: Asia Idioma: Inglés Revista: Journal of Veterinary Science Año: 2019 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Fenobarbital / Taiwán / Intrones / Exones / Miembro 1 de la Subfamilia B de Casetes de Unión a ATP / Análisis de Secuencia por Matrices de Oligonucleótidos / Quimioterapia / Alelos / Genotipo / Métodos Tipo de estudio: Estudio diagnóstico Límite: Animales País/Región como asunto: Asia Idioma: Inglés Revista: Journal of Veterinary Science Año: 2019 Tipo del documento: Artículo