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J. Vet. Sci. 2019; 20(1): 27-33  https://doi.org/10.4142/jvs.2019.20.1.27
Development of an oligonucleotide microarray for simultaneous detection of two canine MDR1 genotypes and association between genotypes and chemotherapy side effects
Jih-Jong Lee, Han-You Lin, Chun-An Chen, Chen-Si Lin, Lih-Chiann Wang*
School of Veterinary Medicine, National Taiwan University, Taipei 10617, Taiwan
Correspondence to: *Tel: +886-2-2739-6828; Fax: +886-2-2732-3817; E-mail: lcwang@ntu.edu.tw
The first two authors contributed equally to this work.
Received: July 17, 2018; Revised: September 30, 2018; Accepted: November 6, 2018; Published online: January 31, 2019.
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.
Keywords: Canine, Chemotherapy, MDR1 gene, Oligonucleotide microarray, P-glycoprotein


© 2019 The Korean Society of Veterinary Science.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.