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Frontiers in veterinary science2023; 10; 1188633; doi: 10.3389/fvets.2023.1188633

Genetic analysis of the equine orthologues for human CYP2D6: unraveling the complexity of the CYP2D family in horses.

Abstract: Because of their importance as companion animals or as racehorses, horses can be treated with various drugs. Although it is known that drug withdrawal times can vary for each horse, pharmacogenetics for these animals has not been adequately studied and requires further development. Since is responsible for the metabolism of 25-30% of drugs in humans, including some used to treat horses, a study of the family in horses was conducted to define its genetic structure as well as its expression pattern in the liver. Unassigned: Genomic DNA extracted from venous blood and mRNA from fresh liver tissue were amplified and sequenced to analyze the genomic structure, genotype, and expression of the various enzymes that are part of the equine orthologous family for . Unassigned: Amplification and sequencing of the gDNA of , the major orthologue identified in previous studies, revealed a novel putative genomic structure for this gene compared with that reported from the EquCab3.0 assembly, including the formation of a hybrid structure similar to what happens in human . At the mRNA level, transcripts from six different members of the equine family were detected in horse liver. In addition, genotyping of and revealed the presence of several polymorphisms, six of which result in novel, nonsynonymous amino acid changes for each of the two genes. Unassigned: This study aimed to elucidate the pharmacogenetic analysis of the family in horses and resulted in the identification of a novel gene structure for , the expression of six different members of the family in horse liver, and several novel polymorphisms for and .
Publication Date: 2023-10-19 PubMed ID: 37929279PubMed Central: PMC10620600DOI: 10.3389/fvets.2023.1188633Google Scholar: Lookup
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  • Journal Article

Summary

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This research focused on investigating the genetic structure and expression pattern of the CYP2D family in horses, which is important in drug metabolism. The study provides new insights into the pharmacogenetics of horses, including the identification of a novel gene structure and several previously unidentified polymorphisms.

Objective and Importance of the Study

  • The study was initiated due to the understanding that horses, often used as race or companion animals, are regularly given various drugs, and their drug withdrawal times can be different for each individual.
  • CYP2D family, known for playing a critical role in the metabolism of 25-30% drugs in humans, is believed to exhibit a similar function in horses, making it a significant genetic feature to study to understand the pharmacogenetics of horses better.

Detailed Procedure of the Study

  • The researchers started by extracting Genomic DNA from venous blood and mRNA from fresh liver tissue of the horses, which was then amplified and sequenced.
  • This process led to the analysis of the genomic structure, different genotypes, and the expression of various enzymes that are part of the equine CYP2D family.

Major Findings

  • Through the amplification and sequencing of the genomic DNA of CYP2D50, an essential orthologue previously identified, a unique putative genomic structure for this gene was discovered, which differs from the previously reported structure from the EquCab3.0 assembly.
  • The novel structure showcased the formation of a hybrid structure, similar to the dynamics observed in human CYP2D6.
  • At the mRNA level, transcripts from six different members of the equine CYP2D family were detected in the horse liver.
  • On genotyping the CYP2D50 and CYP2D54, multiple polymorphisms were found, six of which resulted in new, nonsynonymous amino acid changes for both genes.

Conclusion

  • This research was crucial in providing an in-depth pharmacogenetic analysis of the CYP2D family in horses.
  • It led to the identification of a novel genomic structure for CYP2D50, the expression of six different members of the CYP2D family in horse liver, and several diverse polymorphisms in CYP2D50 and CYP2D54.

Cite This Article

APA
Scantamburlo G, Nofziger C, Paulmichl M, Vanoni S. (2023). Genetic analysis of the equine orthologues for human CYP2D6: unraveling the complexity of the CYP2D family in horses. Front Vet Sci, 10, 1188633. https://doi.org/10.3389/fvets.2023.1188633

Publication

ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 10
Pages: 1188633
PII: 1188633

Researcher Affiliations

Scantamburlo, Giada
  • Pharmgenetix GmbH, Niederalm-Anif, Austria.
Nofziger, Charity
  • Pharmgenetix GmbH, Niederalm-Anif, Austria.
Paulmichl, Markus
  • Privatklinik Maria Hilf GmbH, Klagenfurt, Austria.
Vanoni, Simone
  • Pharmgenetix GmbH, Niederalm-Anif, Austria.

Conflict of Interest Statement

GS, CN and SV are employees of PharmGenetix GmbH. MP is employed by Privatklinik Maria Hilf GmbH.

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