VKORC1 single nucleotide polymorphisms in rodents in Spain

• Published in: Chemosphere
• Main Authors: Bermejo-Nogales, Azucena, Rodríguez Martín, José Antonio, Coll Morales, Julio, Navas Antón, José María
• Other Authors: Ministerio para la Transición Ecológica y el Reto Demográfico (España), CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Agencia Estatal de Investigación (España)
• Format: Article in Journal/Newspaper
• Language: English
• Published: Elsevier 2022
• Subjects: Anticoagulant rodenticides; Binding predictions; Rodents; Spanish vkorc1 mutants; Rattus rattus
• Online Access: http://hdl.handle.net/10261/296733; https://doi.org/10.1016/j.chemosphere.2022.136021; https://doi.org/10.13039/501100011033; https://api.elsevier.com/content/abstract/scopus_id/85137010348

10 Pág. Departamento de Medio Ambiente y Agronomía Rodents are considered one of the animal pests with the greatest impact on agricultural production and public health. Anticoagulant rodenticides (ARs), used as one of the most effective ways to control rodent populations worldwide, inhibit the vitamin K 2,3-epoxide reductase (VKORC1) enzyme involved in blood coagulation. Resistances to ARs are mainly associated with mutations or single nucleotide polymorphisms (SNPs) in the vkorc1 gene. Since the information on this subject is scarce in Spain, we monitored and discovered rodent SNPs that could favour genetic resistance in its populations. For that, more than 200 samples of stools and tails from brown rat (Rattus norvegicus), black rat (Rattus rattus) and mouse (Mus musculus) were collected from 12 Spanish regions previously identified with low AR efficacy in coordination with the National Association of Environmental Sanitation Companies (ANECPLA) and the managing entities of four locations. We then sequenced their vkorc1 exon 3 corresponding genomic DNA. We identified genotypic vkorc1 variations corresponding to amino acid changes at the VKORC1 protein at the S149I - S149T and the E155K - E155Q mutations, depending on the rodent species. Computational analysis of binding predictions found out that the brown rat S149I mutation predicted a high reduction of the binding affinity of chlorophacinone and brodifacoum ARs while, the black rat S149T, E155K and E155Q mutations slightly reduced bromadiolone AR binding. These results suggest that these mutations may be one of the causes of the increased resistance to those ARs. This research was funded by a charge of the Ministry for Ecological Transition and Demographic Challenge to Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), charge number EG17-017 and the project PID2019-108053RJ-I00/AEI/10.13039/501,100,011,033 funded by the Agencia Estatal de Investigación (AEI) Peer reviewed