Identification of genetic variations in μ opioid receptor in cats.

Abstract

μ-opioid receptor (MOP) plays a critical role in mediating opioid analgesic effects. Genetic variations, particularly those in the MOP gene (Oprm1), significantly influence individual variations in opioid efficacy and side effects across species, highlighting the need for pharmacogenomic research in human and veterinary contexts. This study aimed to identify single-nucleotide variations (SNVs) within Oprm1 in 100 cats of various breeds. Oprm1 spans over 170 kb and consists of five exons that combine to yield three splice variants in the cat Ensembl database. Among these variants, Oprm1-202 is an ortholog of the MOR-1 transcript, which is the most abundant in humans and mice. Oprm1-202 shares 92% and 87% coding sequences (CDS) and 96% and 94% amino acid sequence identity with human and mouse MOR-1, respectively. Phylogenetic trees were constructed from the CDS and amino acid sequences of nine species, including humans, cats, and mice. Both the CDS and amino acid sequences of MOP in cats showed phylogenetic development closer to that of primates than of rodents. Four SNVs were identified in the CDS of Oprm1. One SNV was located in exon 1 and the other three in exon 2 of Oprm1, all of which were synonymous substitutions. Although synonymous mutations generally have a limited functional impact, they may influence splicing and receptor expression. Further research is required to assess the effects of these SNVs on opioid efficacy, receptor expression, and analgesic responses across breeds, considering the potential breed-specific genetic factors in cat species.