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• W4377968886 abstract "The pleiotropic effects of the melanocortin system show promise in overcoming limitations associated with large variations in opioid analgesic effectiveness observed in equine practice. Of particular interest is the melanocortin-1-receptor gene (MC1R), which influences melanin type through its epistatic interaction with the agouti signaling protein gene (ASIP), dictating the production of black or red pigment. MC1R has previously been associated with opioid effectiveness in other species; however, evidence of similar relationships in horses is lacking. As such, this study investigated if associations between opioid response and pigmentation genes were also observable in horses. Nociceptive response data were opportunistically collected during the performance of spinal fluid centesis (SFC), noting the pain response of individual horses after sedation. A target dosage range of 0.01–0.02 mg/kg body weight intravenously was used in the administration of the opioid hydromorphone, the primary drug of interest in this study. Genomic regions responsible for the bay (ASIP) and chestnut (MC1R) coat colors were extracted from genome sequence data, and opioid analgesic effectiveness was scored (1–3) based on pain response for each horse (n = 48). Haplotype and SNP association analyseswere performed using the SNPassoc (testing multiple models) and haplo.stats packages and generalized linear models within the statistical software R. Age, breed, sex, and dosage rates were recorded as covariates. Breeds with less than 2 horses were excluded from analyses. Six single-nucleotide polymorphisms (SNPs) within ASIP and one within MC1R were identified as significantly (P < 0.05) associated with opioid analgesic effectiveness during SFC. Haplotype analysis of the significant ASIP SNPs revealed that the most common ASIP haplotype was associated with lower opioid analgesic effectiveness, both in isolation and when looked at in conjunction with MC1R. The recessive MC1Re/e mutation resulting in the production of red pigment only was also significantly associated with decreased opioid analgesic effectiveness. The current study provides promising evidence for important links between pigmentation genes and opioid effectiveness in horses. However, given the complexity of opioid metabolism and the opportunistic nature of the current study, additional investigations are needed if precision medicine approaches are to become a reality in equine veterinary medicine." @default.
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• W4377968886 date "2023-05-01" @default.
• W4377968886 modified "2023-10-17" @default.
• W4377968886 title "47 Investigating links between pigmentation genes and opioid effectiveness in horses" @default.
• W4377968886 doi "https://doi.org/10.1016/j.jevs.2023.104349" @default.
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