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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.
Article Dans Anglais | 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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Texte intégral: Disponible Indice: WPRIM (Pacifique occidental) Sujet Principal: Phénobarbital / Taïwan / Introns / Exons / Glycoprotéine P / Séquençage par oligonucléotides en batterie / Traitement médicamenteux / Allèles / Génotype / Méthodes Type d'étude: Etude diagnostique Limites du sujet: Animaux Pays comme sujet: Asie langue: Anglais Texte intégral: Journal of Veterinary Science Année: 2019 Type: Article

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Texte intégral: Disponible Indice: WPRIM (Pacifique occidental) Sujet Principal: Phénobarbital / Taïwan / Introns / Exons / Glycoprotéine P / Séquençage par oligonucléotides en batterie / Traitement médicamenteux / Allèles / Génotype / Méthodes Type d'étude: Etude diagnostique Limites du sujet: Animaux Pays comme sujet: Asie langue: Anglais Texte intégral: Journal of Veterinary Science Année: 2019 Type: Article