Genotypic and allelic frequencies of MDR1 gene in dogs in Italy

Abstract

BackgroundA mutation in the canine multidrug resistance MDR1 gene (also referred as ABCB1), encoding for the multidrug resistance (MDR) P-glycoprotein (P-gp) transponder, causes a pathological condition known as ‘ivermectin toxicosis’. The causative mutation, known since 2001, has been described to affects sheep herding breeds related to collie lineage. The present study is a retrospective investigation of the presence of MDR1 mutated allele in Italian dog populations in a 5 years’ time lapse. The aim of the research is to offer a deep knowledge in MDR1 allelic and genotypic frequencies in canine breeds and populations raised in Italy.MethodsGenotype data for the 4-bp deletion (c296_299del4) in MDR1 gene from 811 dogs belonging to 32 breeds/populations were collected.ResultsThe mutated allele has been found in 9 out of 31 breeds: Rough Collie, Smooth Collie, Border Collie, Bearded Collie, Shetland Sheepdog, Australian Shepherd, White Swiss Shepherd, Old English Sheepdog, Whippet and also in crossbreed. The breeds with the highest allelic mutation frequency are Smooth and Rough Collies with 75 per cent and 66 per cent of mutant MDR1 allele, respectively.ConclusionsThe results support the usefulness of this genetic analysis to optimise medical care in dogs at risk of multidrug resistance and to create an objective basis in breeding programme definition and in the risk evaluation in different breeds.

Prevalence of the MDR1 gene mutation in herding dog breeds and Thai Ridgebacks in Thailand

“…Although the population of Rough Collies in the current survey was relatively small, as it is an unusual dog breed in Thailand, the current results are similar to those from large-scale studies in the USA, where the mutation frequency was 54.6-56% [ 15 , 16 ]. Moreover, our findings agree with those from several studies from Japan [ 17 ], Brazil [ 18 ], South Africa [ 19 ], Australia [ 20 ], Germany [ 14 , 21 , 22 ], France [ 23 ], the UK [ 24 ], Belgium [ 25 ], Italy [ 26 ], and numerous European countries [ 27 ], where the mutation frequency was estimated to be 50-71%. In Israel, however, a lower mutation frequency of approximately 27.5% was found [ 28 ].…”

“…However, a higher mutation frequency and wide variation have been reported in various other countries, which may be attributed to the different sample sizes of those studies. As stated in large-scale MDR1 genotyping surveys, the mutation frequency was approximately 19.50-22% in Germany [ 21 , 22 ] and 29% in the USA [ 16 ], and a mutation frequency of approximately 25-46% has been reported in the small-to-medium-scale populations investigated in Israel [ 28 ], Japan [ 17 ], South Africa [ 19 ], Australia [ 20 ], and several European countries [ 24 , 26 , 27 ]. In terms of the universal distribution of MDR1 nt230(del4), the second most affected breed is most likely the Australian Shepherd.…”

“…Our study suggests a slightly higher mutation frequency than that in the USA (7-8.4%) [ 15 , 16 ], as well as that reported in Japan [ 17 ] and Brazil [ 18 ] (1.2% and 7.9%, respectively). Much higher mutation frequencies, ranging from 23% to 39.3%, have been described in Israel [ 28 ] and numerous countries in Europe [ 21 , 22 , 24 , 26 , 27 ], other than Austria, where the frequency was 14.5% [ 27 ]. Based on the geographic distribution of MDR1 mutation, there is likely a high prevalence of homologous mutations in Shetland Sheepdogs across European countries.…”

“…This discrepancy may be due to the small sample size in our study. In European countries, mutation frequencies reported in Germany [ 21 , 22 ] and Italy [ 26 ] varied from 4% to 7.5%, whereas a higher mutation frequency of approximately 11.5% has been described in UK [ 24 ]. In Brazil, however, the presence of MDR1 nt230(del4) was not identified in this breed [ 18 ].…”

Clinical and Laboratory Findings in Dogs Undergoing Adjuvant Chemotherapy with Gemcitabine/Carboplatin Combination for Mammary Neoplasia

“…In addition, the same canine had 3 thrombocytopenic events (one grade 1 episode in E5 and two grade 2 events in E2 and E3) and was one out of the two dogs that had vomiting (grade 2) and diarrhea (grade 1) after the first chemotherapy session. Border Collie breed dogs may have polymorphisms (Alves et al, 2011) and even nt230 (del4) ABCB1 gene mutation (Dekel et al, 2017;Marelli et al, 2020), interfering with glycoprotein P substrates metabolism. Several chemotherapeutic agents have already been identified as substrates of the glycoprotein P (Mealey, 2004;Linardi and Natalini, 2006;Mealey et al, 2017), but gemcitabine and carboplatin were not so far.…”