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

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저자정보: Jih-Jong Lee (National Taiwan University) Han-You Lin (National Taiwan University) Chun-An Chen (National Taiwan University) Chen-Si Lin (National Taiwan University) Lih-Chiann Wang (National Taiwan University)

저널정보: 대한수의학회 Journal of Veterinary Science Journal of Veterinary Science 제20권 제1호

발행연도: 2019.1

수록면: 27 - 33 (7page)

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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.

#Canine #Chemotherapy #MDR1 gene #Oligonucleotide microarray #P-glycoprotein

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