Dataset Information

Genotypic and allelic frequencies of MDR1 gene in dogs in Italy.

ABSTRACT: Background:A 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. Methods:Genotype data for the 4-bp deletion (c296_299del4) in MDR1 gene from 811 dogs belonging to 32 breeds/populations were collected. Results:The 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. Conclusions:The 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.

SUBMITTER: Marelli SP

PROVIDER: S-EPMC7319724 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Genotypic and allelic frequencies of MDR1 gene in dogs in Italy.

Marelli Stefano Paolo SP Polli Michele M Frattini Stefano S Cortellari Matteo M Rizzi Rita R Crepaldi Paola P

Veterinary record open 20200624 1

<h4>Background</h4>A 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 po ...[more]

PMID: 32617164

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Project description:The inflammatory response plays a key role at different stages of cancer development. Allelic variants of the interleukin 1A (IL1A), interleukin 4 (IL4), nuclear factor kappa B1 (NFKB1) and protease-activated receptor 1 (PAR1) genes may influence not only the inflammatory response but also susceptibility to cancer development. Among major ethnic or continental groups, these polymorphic variants present different allelic frequencies. In admixed populations, such as the Brazilian population, data on distribution of these polymorphisms are limited. Here, we collected samples of cancer-free individuals from the north, northeast, midwest, south and southeast regions of Brazil and from the three main groups that gave rise to the Brazilian population: Native Americans from the Brazilian Amazon, Africans and Europeans. We describe the allelic distributions of four IL1A (rs3783553), IL4 (rs79071878), NFKB1 (rs28362491) and PAR1 (rs11267092) gene polymorphisms, which the literature describes as polymorphisms with a risk of cancer or worse prognosis for cancer.The genotypic distribution of the four polymorphisms was statistically distinct between Native Americans, Africans and Europeans. For the allelic frequency of these polymorphisms, the Native American population was the most distinct among the three parental populations, and it included the greatest number of alleles with a risk of cancer or worse prognosis for cancer. The PAR1 gene polymorphism allelic distribution was similar among all Brazilian regions. For the other three markers, the northern region population was statistically distinct from other Brazilian region populations.The IL1A, IL4, NFKB1 and PAR1 gene polymorphism allelic distributions are homogeneous among the regional Brazilian populations, except for the northern region, which significantly differs from the other four Brazilian regions. Among the parental populations, the Native American population exhibited a higher incidence of alleles with risk of cancer or worse prognosis for cancer, which can indicate greater susceptibility to this disease. These genetic data may be useful for future studies on the association between these polymorphisms and cancer in the investigated populations.

Project description:AIMS: To investigate the frequency of the single nucleotide polymorphism C3435T in exon 26 of the MDR1 gene in Asians and to determine the functional significance of this SNP with the clinical pharmacokinetics of oral cyclosporin (Neoral) in 10 stable heart transplant patients. METHODS: The MDR1 C3435T polymorphism was investigated in 290 healthy Asian subjects (98 Chinese, 99 Malays and 93 Indians). We also compared the MDR1 polymorphism between the Asian population studied here and the published data on Africans and Caucasians. The clinical relevance of this SNP on oral bioavailability of a known P-gp substrate, cyclosporin, was assessed in 10 stable Chinese heart transplant patients. RESULTS: The homozygous TT genotype was observed in 32%, 28% and 43% of Chinese, Malays and Indians. The homozygous CC genotype was found in 25% of Chinese and Malays compared with 18% of Indians. The Indians had a lower frequency of the C allele [0.38 (0.31-0.45)] compared with the Chinese [0.46 (0.39-0.53)] and Malays [0.48 (0.42-0.55)]. Chi-squared test showed that the distribution of allele frequencies between the Malays and Indians differed significantly (P = 0.04). In this Asian population, the overall distribution of genotypes (CC, CT and TT) and allele frequencies were significantly different from those in Africans (P < 0.001). The results were also significant when the Chinese, Malays and Indians were compared separately with the African group (P < 0.001). Compared with the Caucasian data, the overall distribution of genotype and allele frequencies in the Asian population were also significantly different (P < or = 0.05). However, when each Asian ethnic group was compared separately with the Caucasians, only the Indians were found to be significantly different (P < or = 0.004). Genotypic-phenotypic correlations of this SNP were assessed in 10 stable Chinese heart transplant patients. The median AUC(0,4 h) was 11% lower in patients with CC genotype compared with subjects with TT genotype. However, the interpatient variability in AUC(0,4 h) was high in patients, especially in those with CC genotype. CONCLUSIONS: The distribution of the SNP C3435T in exon 26 in the Chinese and Malay population was found to be similar to the Caucasians whereas the Indians were different. The Asian population also differed significantly from the African and Caucasian population in the distribution of the C3435T SNP. The low frequency of the T allele in the Indian population implies lower expression of P-gp and may have important therapeutic and prognostic implications for use of P-gp dependent drugs in individuals of Indian origin.

Dataset Information

Genotypic and allelic frequencies of MDR1 gene in dogs in Italy.

Publications

Genotypic and allelic frequencies of <i>MDR1</i> gene in dogs in Italy.

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