biostudies-literaturePeng SNational Center for Advancing Translational SciencesNCATS NIH HHSUC Davis Center for Equine HealthSouthern California Equine Foundation2203-2212https://www.ebi.ac.uk/biostudies/studies/S-EPMC9708438biostudies-literatureUnknown36(6)<h4>Background</h4>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.<h4>Hypothesis/objectives</h4>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.<h4>Animals</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions and clinical importance</h4>An underlying genetic etiology may exist for high GGT syndrome in racing TBs, similar to genetic disorders in humans.Journal of veterinary internal medicineInvestigation of high gamma-glutamyltransferase syndrome in California Thoroughbred racehorses.PMC9708438L40 TR001136NABlea JMagdesian KGCarpenter RPeng SHo WFinno CJDowd JfalseInvestigation of high gamma-glutamyltransferase syndrome in California Thoroughbred racehorses.<h4>Background</h4>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.<h4>Hypothesis/objectives</h4>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.<h4>Animals</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions and clinical importance</h4>An underlying genetic etiology may exist for high GGT syndrome in racing TBs, similar to genetic disorders in humans.2022-01-01T00:00:00Z2022 Nov2026-06-21T03:17:04.667Z2025-04-07T06:21:26.167ZS-EPMC97084383637765210.1111/jvim.16582