Pharmacogenetics in veterinary precision medicine: dream or reality?

The term pharmacogenetics (PGx) integrates the field of genetics and pharmacology with the aim of investigating the effect of an individual genotype on the pharmacokinetics and pharmacodynamics (PK/PD) of drugs. This discipline, fuelled by recent cutting-edge sequencing technologies, led to the gradual shift from the traditional approach of “one drug fits all” to a more personalized, patient-oriented treatment, defined as precision medicine [1]. At present, 68 clinically important human pharmacogenes, including phase I and II drug-metabolizing enzymes, transporters, drug targets and oncogenes, have been identified [2]. Human cytochromes P450 (CYPs), the most studied pharmacogenes, are highly polymorphic, and CYP polymorphisms are associated to significant adverse drug reactions, lack of response to treatment and inter-individual variability in drug response [3]. PGx is a somewhat new discipline in veterinary medicine (VM); even though significant strides have been made in the past 20 years, it is still in its infancy compared to the human counterpart [4]. Most of data concern the canine species for its importance in pre-clinical and clinical sciences. A well-known example is the ABCB1 deletion polymorphism in Collie dogs and other herding dog breeds causing fatal reactions to many P-glycoprotein substrates [5]. Moreover a CYP1A2 stop codon polymorphism, whose prevalence varies considerably between and within dog breeds, has been described [6]. Conversely, few examples of PGx application in food-producing species are available. Apart from polymorphisms influencing PK (e.g., ABCG2 Tyr581Ser in dairy cows and CYP3A28 Gly197Ser in meat cattle [7-8]), most of identified variants are usually associated to productivity traits. Since PGx shows a wide range of applications and undoubted benefits, more efforts have to be made to develop its use in VM and promote an individualized therapy approach; to reach this goal, large scale genetic data are needed and the functional impact of pharmacogene variants must be characterized