PDF(Pubmed)
Abstract：
BACKGROUND: 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 variation in the melanocortin-1-receptor (MC1R) gene, which dictates pigment type expression through its epistatic interaction with the agouti signalling protein (ASIP) gene. MC1R has previously been implicated in opioid efficacy in other species; however, this relationship is yet to be explored in horses. In this study, analgesic effectiveness was scored (1-3) based on noted response to dura penetration during the performance of cerebrospinal fluid centisis after sedation and tested for association with known genetic regions responsible for pigmentation variation in horses.
RESULTS: The chestnut phenotype was statistically significant (P < 0.05) in lowering analgesic effectiveness when compared to the bay base coat colour. The 11bp indel in ASIP known to cause the black base coat colour was not significant (P>0.05); however, six single nucleotide polymorphisms (SNPs) within the genomic region encoding the ASIP gene and one within MC1R were identified as being nominally significant (P<0.05) in association with opioid analgesic effectiveness. This included the location of the known e MC1R variant resulting in the chestnut coat colour.
CONCLUSIONS: The current study provides promising evidence for important links between pigmentation genes and opioid effectiveness in horses. The application of an easily identifiable phenotype indicating variable sensitivity presents a promising opportunity for accessible precision medicine in the use of analgesics and warrants further investigation.
RESULTS: The chestnut phenotype was statistically significant (P < 0.05) in lowering analgesic effectiveness when compared to the bay base coat colour. The 11bp indel in ASIP known to cause the black base coat colour was not significant (P>0.05); however, six single nucleotide polymorphisms (SNPs) within the genomic region encoding the ASIP gene and one within MC1R were identified as being nominally significant (P<0.05) in association with opioid analgesic effectiveness. This included the location of the known e MC1R variant resulting in the chestnut coat colour.
CONCLUSIONS: The current study provides promising evidence for important links between pigmentation genes and opioid effectiveness in horses. The application of an easily identifiable phenotype indicating variable sensitivity presents a promising opportunity for accessible precision medicine in the use of analgesics and warrants further investigation.
摘要：
背景：黑皮质素系统的多效性有望克服与马实践中观察到的阿片类镇痛效果的大差异相关的局限性。特别感兴趣的是黑皮质素-1受体（MC1R）基因的变异，它通过与刺鼠信号蛋白（ASIP）基因的上位相互作用来决定色素类型的表达。MC1R以前曾与其他物种的阿片类药物功效有关；然而，这种关系尚未在马匹中探索。在这项研究中,镇痛效果评分(1-3)基于在镇静后执行脑脊液刺激期间对硬脑膜渗透的反应,并测试与导致马色素沉着变异的已知遗传区域的关联.
结果：与海湾底涂层颜色相比，栗子表型在降低镇痛效果方面具有统计学意义（P<0.05）。ASIP中已知引起黑色基色的11bpindel并不显著(P>0.05)；然而，编码ASIP基因的基因组区域内的6个单核苷酸多态性(SNPs)和MC1R内的1个单核苷酸多态性被鉴定为与阿片类药物镇痛效果相关的标称显著(P<0.05).这包括导致栗色的已知eMC1R变体的位置。
结论：当前的研究为马的色素沉着基因与阿片类药物有效性之间的重要联系提供了有希望的证据。应用表明可变敏感性的易于识别的表型为使用镇痛药提供了可获得的精准医学的有希望的机会，并值得进一步研究。
结果：与海湾底涂层颜色相比，栗子表型在降低镇痛效果方面具有统计学意义（P<0.05）。ASIP中已知引起黑色基色的11bpindel并不显著(P>0.05)；然而，编码ASIP基因的基因组区域内的6个单核苷酸多态性(SNPs)和MC1R内的1个单核苷酸多态性被鉴定为与阿片类药物镇痛效果相关的标称显著(P<0.05).这包括导致栗色的已知eMC1R变体的位置。
结论：当前的研究为马的色素沉着基因与阿片类药物有效性之间的重要联系提供了有希望的证据。应用表明可变敏感性的易于识别的表型为使用镇痛药提供了可获得的精准医学的有希望的机会，并值得进一步研究。
