VKORC1 mutation in European populations of Rattus norvegicus with first data for Italy and the report of a new amino acid substitution

In the Norway rat, Rattus norvegicus, anticoagulant rodenticide resistance is mainly associated with mutations in the third exon of the Vitamin K epoxide reductase complex subunit 1 (VKORC1). Identification of the resistant wild populations is very important to improve the control practices and to limit the damages due to inadequate use of the anticoagulant rodenticide. In this study, we determined the distribution of the third exon mutations in poorly investigated areas of Africa, Europe and the Middle East. In particular, we investigated the phenomenon for the first time in the Italian peninsula. We obtained sequences of the third exon for 133 Norway rats from 37 localities in Africa, Europe and the Middle East. For additional analysis, we retrieved information in literature on amino acid substitution in 1136 third exon sequences of Norway rats from Europe, the Far East, North America and South America. However, we found third exon mutations only in Europe and the Far East with the Y139F mutation shared between the two areas. Europe has the higher number of mutant individuals and Y139C mutation prevails. In Italy, we found a single missense mutation (I123S) in a Venetian locality. This homozygote mutation, is not know in literature to be associated with resistance, but it is very similar to a mutation that confers resistance in humans (I123N). This similarity and its high local frequency makes it a good candidate for future testing. Our results provide useful data to better understand the resistance phenomenon and to plan targeted control actions.