Incidence of Vkorc1 gene mutations in brown rat (Rattus norvegicus) populations from downtown Madrid and their role in resistance to anticoagulant rodenticide: Implications for rodenticide management
Year: 2026
Type: article
Abstract: The brown rat ( Rattus norvegicus ) is considered a pest and the use of anticoagulant rodenticides (ARs) has been considered a valuable method for their management. ARs inhibit the enzyme vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1), preventing activation of coagulation factors and provoking death by internal bleeding. Resistance to ARs is associated to Vkorc1 gene mutations. In the present study, we aim to characterize the incidence of mutations in Madrid downtown by using a novel sampling approach, based on a systematic procedure. Madrid central core (approx. 42 km 2 ) was divided in a grid with quadrants of one Km 2 each and 21 alternating quadrants were selected. Stool samples were collected (120 in total) for DNA extraction and sequencing of targeted genes. The Ser149Ile (S149I) mutation was more frequent in the south and the Glu155Lys (E155K, described for the first time in Spanish brown rats) in the north of the city while double mutants were found in the central area. A geospatial study was performed to relate population density, rat warnings, bromadiolone use and trash production with Vkorc1 mutation frequency. No statistically significant correlations were found, but the higher mutation frequency appeared in areas with higher trash production. Interestingly, the generated mutation frequency map will facilitate the effective management of ARs application by accounting for resistance evolution, serving as a valuable tool to enhance rodent control strategies. Docking analysis was done for comparing mutation effects on VKORC1 sensitivity to ARs showing differences among genotypes binding affinities towards vitamin K and ARs. • Systematic sampling is a new approach to discover all genotypes and their frequency of all incidence areas • We found the S149I and E155K mutations, the latter described for the first time in Spain. • A tendency of high mutation frequency and trash production is detected in maps • VKORC1 mutations have a specific signature of binding affinity to AR • Vitamin K binding affinity of the S149I mutation is reduced while E155K is enhanced
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,650
Awards: G3598324095, G770836728
OpenAlex ID: W7119512313