Association Between the nt230(del4) Mutation and c.-6-180T>G Polymorphism in the Canine ABCB1 Gene

A 4-base pair deletion in the ABCB1 (MDR1) gene, resulting in a frameshift and truncated, nonfunctional P-glycoprotein, is frequently observed in certain dog breeds and is known to cause drug sensitivity. Another variant, a single nucleotide substitution (c.-6-180T > G) located near the gene's promoter region, has also been identified; however, its clinical significance remains unclear. This study aimed to determine the genotype distribution of the nt230(del4) deletion and the c.-6-180T > G substitution across various dog breeds and to evaluate whether an association exists between these variants. A total of 263 client-owned dogs from 17 breeds were genotyped for both mutations. Genomic DNA was extracted using a spin column-based method. The deletion was detected using a modified allele-specific real-time PCR assay, and the SNP was assessed via PCR followed by RFLP analysis. The nt230(del4) mutation was identified exclusively in collie-lineage breeds, including collie, Shetland sheepdog, Australian shepherd, bobtail, and white Swiss shepherd. The c.-6-180T > G SNP was widespread across all breeds, with a G allele frequency of 35%. Genotype distribution included 111 T/T homozygotes, 119 T/G heterozygotes, and 33 G/G homozygotes. Notably, all individuals carrying the deletion also possessed at least one G allele, suggesting a co-occurrence between the two variants. The observed association between the nt230(del4) deletion and the c.-6-180T > G SNP in this cohort may reflect shared ancestry and/or local linkage disequilibrium. Further research is warranted to explore the functional consequences of this SNP and its potential role in canine drug response.