Investigation of high gamma‐glutamyltransferase syndrome in California Thoroughbred racehorses
Abstract Background Increases in serum gamma‐glutamyltransferase (GGT) activity have been reported in Thoroughbred (TB) racehorses and associated with maladaptation to training but the underlying etiology remains unknown. Hypothesis/Objectives Classify the etiology of high GGT syndrome in racing TBs...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-11-01
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| Series: | Journal of Veterinary Internal Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/jvim.16582 |
| _version_ | 1797976862180245504 |
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| author | Sichong Peng K. Gary Magdesian Joseph Dowd Jeffrey Blea Ryan Carpenter Wayne Ho Carrie J. Finno |
| author_facet | Sichong Peng K. Gary Magdesian Joseph Dowd Jeffrey Blea Ryan Carpenter Wayne Ho Carrie J. Finno |
| author_sort | Sichong Peng |
| collection | DOAJ |
| description | Abstract Background Increases in serum gamma‐glutamyltransferase (GGT) activity have been reported in Thoroughbred (TB) racehorses and associated with maladaptation to training but the underlying etiology remains unknown. Hypothesis/Objectives Classify the etiology of high GGT syndrome in racing TBs by assessment of pancreatic enzymes, vitamin E concentrations, and both a candidate gene and whole genome association study. We hypothesized that a genetic variant resulting in antioxidant insufficiency or pancreatic dysfunction would be responsible for high GGT syndrome in TBs. Animals A total of 138 California racing TBs. Amylase: n = 31 affected (serum GGT activity ≥60 IU/L), n = 52 control (serum GGT activity <40 IU/L). Lipase: n = 19 affected, n = 35 control. Serum α‐tocopherol concentrations: n = 32 affected, n = 46 control. Genome‐wide association study (GWAS): 36 affected, 58 control. Whole genome sequencing: n = 5 affected, n = 5 control. Methods Biochemical and vitamin analytes were compared among cohorts. A GWAS was performed and a subset of TBs underwent whole genome sequencing to interrogate candidate genes and positional genetic regions. Results Serum lipase and amylase activity and α‐tocopherol concentrations did not differ between groups. No genetic variants were identified in 2 candidate genes (UGT1A1 and GGT1) that associated with the phenotype. Four single nucleotide polymorphisms (SNPs) approached a suggestive association with the phenotype (P = 2.15 × 10−5), defining a 100 kb region on chromosome 5 surrounding cluster of differentiation 1a (CD1A1), a transmembrane gene related to the major histocompatibility complex. Conclusions and Clinical Importance An underlying genetic etiology may exist for high GGT syndrome in racing TBs, similar to genetic disorders in humans. |
| first_indexed | 2024-04-11T04:57:43Z |
| format | Article |
| id | doaj.art-7c5023ad95834deb89dbd3ba1e2900f8 |
| institution | Directory Open Access Journal |
| issn | 0891-6640 1939-1676 |
| language | English |
| last_indexed | 2024-04-11T04:57:43Z |
| publishDate | 2022-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Veterinary Internal Medicine |
| spelling | doaj.art-7c5023ad95834deb89dbd3ba1e2900f82022-12-26T07:32:24ZengWileyJournal of Veterinary Internal Medicine0891-66401939-16762022-11-013662203221210.1111/jvim.16582Investigation of high gamma‐glutamyltransferase syndrome in California Thoroughbred racehorsesSichong Peng0K. Gary Magdesian1Joseph Dowd2Jeffrey Blea3Ryan Carpenter4Wayne Ho5Carrie J. Finno6Department of Population Health and Reproduction University of California Davis California USADepartment of Medicine and Epidemiology School of Veterinary Medicine, University of California Davis California USAEquine Medical and Surgical Group Arcadia California USAVon Bleucher, Blea, Hunkin, DVM, Inc Sierra Madre California USADVM Sierra Madre California USASouthern California Equine Foundation Arcadia California USADepartment of Population Health and Reproduction University of California Davis California USAAbstract Background Increases in serum gamma‐glutamyltransferase (GGT) activity have been reported in Thoroughbred (TB) racehorses and associated with maladaptation to training but the underlying etiology remains unknown. Hypothesis/Objectives Classify the etiology of high GGT syndrome in racing TBs by assessment of pancreatic enzymes, vitamin E concentrations, and both a candidate gene and whole genome association study. We hypothesized that a genetic variant resulting in antioxidant insufficiency or pancreatic dysfunction would be responsible for high GGT syndrome in TBs. Animals A total of 138 California racing TBs. Amylase: n = 31 affected (serum GGT activity ≥60 IU/L), n = 52 control (serum GGT activity <40 IU/L). Lipase: n = 19 affected, n = 35 control. Serum α‐tocopherol concentrations: n = 32 affected, n = 46 control. Genome‐wide association study (GWAS): 36 affected, 58 control. Whole genome sequencing: n = 5 affected, n = 5 control. Methods Biochemical and vitamin analytes were compared among cohorts. A GWAS was performed and a subset of TBs underwent whole genome sequencing to interrogate candidate genes and positional genetic regions. Results Serum lipase and amylase activity and α‐tocopherol concentrations did not differ between groups. No genetic variants were identified in 2 candidate genes (UGT1A1 and GGT1) that associated with the phenotype. Four single nucleotide polymorphisms (SNPs) approached a suggestive association with the phenotype (P = 2.15 × 10−5), defining a 100 kb region on chromosome 5 surrounding cluster of differentiation 1a (CD1A1), a transmembrane gene related to the major histocompatibility complex. Conclusions and Clinical Importance An underlying genetic etiology may exist for high GGT syndrome in racing TBs, similar to genetic disorders in humans.https://doi.org/10.1111/jvim.16582amylasegeneticslipasevitamin E |
| spellingShingle | Sichong Peng K. Gary Magdesian Joseph Dowd Jeffrey Blea Ryan Carpenter Wayne Ho Carrie J. Finno Investigation of high gamma‐glutamyltransferase syndrome in California Thoroughbred racehorses Journal of Veterinary Internal Medicine amylase genetics lipase vitamin E |
| title | Investigation of high gamma‐glutamyltransferase syndrome in California Thoroughbred racehorses |
| title_full | Investigation of high gamma‐glutamyltransferase syndrome in California Thoroughbred racehorses |
| title_fullStr | Investigation of high gamma‐glutamyltransferase syndrome in California Thoroughbred racehorses |
| title_full_unstemmed | Investigation of high gamma‐glutamyltransferase syndrome in California Thoroughbred racehorses |
| title_short | Investigation of high gamma‐glutamyltransferase syndrome in California Thoroughbred racehorses |
| title_sort | investigation of high gamma glutamyltransferase syndrome in california thoroughbred racehorses |
| topic | amylase genetics lipase vitamin E |
| url | https://doi.org/10.1111/jvim.16582 |
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