Expression of select mRNA in Thoroughbreds with catastrophic racing injuries

Allen E. Page; Emma Adam; Rick Arthur; Virginia Barker; Forrest Franklin; Ron Friedman; Timothy Grande; Michael Hardy; Bruce Howard; Emma Partridge; Matthew Rutledge; Mary Scollay; John C. Stewart; Alina Vale; David W. Horohov

doi:10.1111/evj.13423

Expression of select mRNA in Thoroughbreds with catastrophic racing injuries

Allen E. Page, Emma Adam, Rick Arthur, Virginia Barker, Forrest Franklin, Ron Friedman, Timothy Grande, Michael Hardy, Bruce Howard, Emma Partridge, Matthew Rutledge, Mary Scollay, John C. Stewart, Alina Vale, David W. Horohov

Veterinary Science

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Background: The ability to identify horses at risk for catastrophic injuries continues to be a pressing issue for the racing industry, especially given recent events in North America. Objectives: Since most catastrophic injuries occur in areas of existing pathology and this pathology is likely to elicit an inflammatory response, it was hypothesised that analysis of messenger RNA (mRNA) expression would detect significant changes in select genes in horses at risk for a catastrophic injury. Study design: Prospective cohort study. Methods: Five racing jurisdictions across the United States participated in this study. A total of 686 Tempus^® RNA Blood Tube samples were collected for mRNA analysis from 107 catastrophically injured horses, as well as from noninjured horses sampled either prerace (n = 374) or postrace (n = 205). A subset of horses (n = 37) were sampled both prerace and postrace for analysis of expression changes during the postrace period. Results: Of 21 genes analysed via RT-qPCR, the expression of 12 genes (ALOX5AP, CD14, IL-10, IL-1β, IL-6, IL-8, MMP1, PTGS2, TLR4, TNFα, TNFSF13B and VEGFA) changed significantly within 45 minutes after a race and were excluded. Of the remaining nine genes (BMP-2, IGF-1, IL1RN, MMP2, MMP9, Osteoprotegrin, RANKL, SAA1 and TGFβ), three genes (IGF-1, IL1RN and MMP2) were found to be significantly different between catastrophically injured and noninjured horses using multiple logistic regression modelling. Receiver operating characteristic analysis of models, which included mRNA expression, demonstrated sensitivities from 76%-82% (95% CI: 67%-93%) and specificities from 84%-88% (95% CI: 71%-94%) at the Youden Index. Main limitations: Samples were collected as soon as possible postinjury (within 30 minutes). Conclusions: Analysis of mRNA expression of specific genes in the future may be considered as an economical, accessible and noninvasive means by which horses at risk for catastrophic injury can be identified.

Original language	English
Pages (from-to)	63-73
Number of pages	11
Journal	Equine Veterinary Journal
Volume	54
Issue number	1
DOIs	https://doi.org/10.1111/evj.13423
State	Published - Jan 2022

Bibliographical note

Funding Information:
This project was funded, in its entirety, by the Kentucky Horse Racing Commission's Equine Drug Research Council. The authors recognise and thank Dr Kathleen Picciano of the New Jersey Racing Commission, as well as the staff of the participating racing jurisdictions and tracks for their assistance with the collection of samples for this project. The authors also thank Dr Arnold Stromberg for his assistance with portions of the statistical analyses.

Publisher Copyright:
© 2021 EVJ Ltd

ASJC Scopus subject areas

Equine

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10.1111/evj.13423

Cite this

@article{121eca0d4ed1489e936da85d4c4e4508,

title = "Expression of select mRNA in Thoroughbreds with catastrophic racing injuries",

abstract = "Background: The ability to identify horses at risk for catastrophic injuries continues to be a pressing issue for the racing industry, especially given recent events in North America. Objectives: Since most catastrophic injuries occur in areas of existing pathology and this pathology is likely to elicit an inflammatory response, it was hypothesised that analysis of messenger RNA (mRNA) expression would detect significant changes in select genes in horses at risk for a catastrophic injury. Study design: Prospective cohort study. Methods: Five racing jurisdictions across the United States participated in this study. A total of 686 Tempus{\textregistered} RNA Blood Tube samples were collected for mRNA analysis from 107 catastrophically injured horses, as well as from noninjured horses sampled either prerace (n = 374) or postrace (n = 205). A subset of horses (n = 37) were sampled both prerace and postrace for analysis of expression changes during the postrace period. Results: Of 21 genes analysed via RT-qPCR, the expression of 12 genes (ALOX5AP, CD14, IL-10, IL-1β, IL-6, IL-8, MMP1, PTGS2, TLR4, TNFα, TNFSF13B and VEGFA) changed significantly within 45 minutes after a race and were excluded. Of the remaining nine genes (BMP-2, IGF-1, IL1RN, MMP2, MMP9, Osteoprotegrin, RANKL, SAA1 and TGFβ), three genes (IGF-1, IL1RN and MMP2) were found to be significantly different between catastrophically injured and noninjured horses using multiple logistic regression modelling. Receiver operating characteristic analysis of models, which included mRNA expression, demonstrated sensitivities from 76%-82% (95% CI: 67%-93%) and specificities from 84%-88% (95% CI: 71%-94%) at the Youden Index. Main limitations: Samples were collected as soon as possible postinjury (within 30 minutes). Conclusions: Analysis of mRNA expression of specific genes in the future may be considered as an economical, accessible and noninvasive means by which horses at risk for catastrophic injury can be identified.",

author = "Page, {Allen E.} and Emma Adam and Rick Arthur and Virginia Barker and Forrest Franklin and Ron Friedman and Timothy Grande and Michael Hardy and Bruce Howard and Emma Partridge and Matthew Rutledge and Mary Scollay and Stewart, {John C.} and Alina Vale and Horohov, {David W.}",

note = "Funding Information: This project was funded, in its entirety, by the Kentucky Horse Racing Commission's Equine Drug Research Council. The authors recognise and thank Dr Kathleen Picciano of the New Jersey Racing Commission, as well as the staff of the participating racing jurisdictions and tracks for their assistance with the collection of samples for this project. The authors also thank Dr Arnold Stromberg for his assistance with portions of the statistical analyses. Publisher Copyright: {\textcopyright} 2021 EVJ Ltd",

year = "2022",

month = jan,

doi = "10.1111/evj.13423",

language = "English",

volume = "54",

pages = "63--73",

number = "1",

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T1 - Expression of select mRNA in Thoroughbreds with catastrophic racing injuries

AU - Page, Allen E.

AU - Adam, Emma

AU - Arthur, Rick

AU - Barker, Virginia

AU - Franklin, Forrest

AU - Friedman, Ron

AU - Grande, Timothy

AU - Hardy, Michael

AU - Howard, Bruce

AU - Partridge, Emma

AU - Rutledge, Matthew

AU - Scollay, Mary

AU - Stewart, John C.

AU - Vale, Alina

AU - Horohov, David W.

N1 - Funding Information: This project was funded, in its entirety, by the Kentucky Horse Racing Commission's Equine Drug Research Council. The authors recognise and thank Dr Kathleen Picciano of the New Jersey Racing Commission, as well as the staff of the participating racing jurisdictions and tracks for their assistance with the collection of samples for this project. The authors also thank Dr Arnold Stromberg for his assistance with portions of the statistical analyses. Publisher Copyright: © 2021 EVJ Ltd

PY - 2022/1

Y1 - 2022/1

N2 - Background: The ability to identify horses at risk for catastrophic injuries continues to be a pressing issue for the racing industry, especially given recent events in North America. Objectives: Since most catastrophic injuries occur in areas of existing pathology and this pathology is likely to elicit an inflammatory response, it was hypothesised that analysis of messenger RNA (mRNA) expression would detect significant changes in select genes in horses at risk for a catastrophic injury. Study design: Prospective cohort study. Methods: Five racing jurisdictions across the United States participated in this study. A total of 686 Tempus® RNA Blood Tube samples were collected for mRNA analysis from 107 catastrophically injured horses, as well as from noninjured horses sampled either prerace (n = 374) or postrace (n = 205). A subset of horses (n = 37) were sampled both prerace and postrace for analysis of expression changes during the postrace period. Results: Of 21 genes analysed via RT-qPCR, the expression of 12 genes (ALOX5AP, CD14, IL-10, IL-1β, IL-6, IL-8, MMP1, PTGS2, TLR4, TNFα, TNFSF13B and VEGFA) changed significantly within 45 minutes after a race and were excluded. Of the remaining nine genes (BMP-2, IGF-1, IL1RN, MMP2, MMP9, Osteoprotegrin, RANKL, SAA1 and TGFβ), three genes (IGF-1, IL1RN and MMP2) were found to be significantly different between catastrophically injured and noninjured horses using multiple logistic regression modelling. Receiver operating characteristic analysis of models, which included mRNA expression, demonstrated sensitivities from 76%-82% (95% CI: 67%-93%) and specificities from 84%-88% (95% CI: 71%-94%) at the Youden Index. Main limitations: Samples were collected as soon as possible postinjury (within 30 minutes). Conclusions: Analysis of mRNA expression of specific genes in the future may be considered as an economical, accessible and noninvasive means by which horses at risk for catastrophic injury can be identified.

AB - Background: The ability to identify horses at risk for catastrophic injuries continues to be a pressing issue for the racing industry, especially given recent events in North America. Objectives: Since most catastrophic injuries occur in areas of existing pathology and this pathology is likely to elicit an inflammatory response, it was hypothesised that analysis of messenger RNA (mRNA) expression would detect significant changes in select genes in horses at risk for a catastrophic injury. Study design: Prospective cohort study. Methods: Five racing jurisdictions across the United States participated in this study. A total of 686 Tempus® RNA Blood Tube samples were collected for mRNA analysis from 107 catastrophically injured horses, as well as from noninjured horses sampled either prerace (n = 374) or postrace (n = 205). A subset of horses (n = 37) were sampled both prerace and postrace for analysis of expression changes during the postrace period. Results: Of 21 genes analysed via RT-qPCR, the expression of 12 genes (ALOX5AP, CD14, IL-10, IL-1β, IL-6, IL-8, MMP1, PTGS2, TLR4, TNFα, TNFSF13B and VEGFA) changed significantly within 45 minutes after a race and were excluded. Of the remaining nine genes (BMP-2, IGF-1, IL1RN, MMP2, MMP9, Osteoprotegrin, RANKL, SAA1 and TGFβ), three genes (IGF-1, IL1RN and MMP2) were found to be significantly different between catastrophically injured and noninjured horses using multiple logistic regression modelling. Receiver operating characteristic analysis of models, which included mRNA expression, demonstrated sensitivities from 76%-82% (95% CI: 67%-93%) and specificities from 84%-88% (95% CI: 71%-94%) at the Youden Index. Main limitations: Samples were collected as soon as possible postinjury (within 30 minutes). Conclusions: Analysis of mRNA expression of specific genes in the future may be considered as an economical, accessible and noninvasive means by which horses at risk for catastrophic injury can be identified.

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Expression of select mRNA in Thoroughbreds with catastrophic racing injuries

Abstract

Bibliographical note

ASJC Scopus subject areas

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