2016 ACVIM Forum Research Abstract Program

Due to its neuronal modulatory actions, our study suggests that oxytocin concentration may be involved in the pathogenesis of NMS and other disorders of the equine neonate. Hyperprogesteronemia was associated with NMS, sepsis, and poor prognosis for survival in hospitalized foals. Equine metabolic syndrome (EMS), a clustering of clinical signs including insulin resistance and dyslipidemia, is the most common cause of laminitis, a painful and life-threatening disease of the horse's hoof. In a large across-breeds study of metabolic variation in horses, our lab demonstrated that EMS phenotypic variability in metabolic traits is influenced by genetic and environmental factors. Further, we demonstrated that certain features of the EMS phenotype are different between breeds. The objective of this project was to identify genomic regions contributing to EMS by performing a genome-wide association study (GWAS) in a cohort of 232 Welsh ponies phenotyped for 11 metabolic traits. Individuals were genotyped on one of two SNP arrays (670,000 to 1,800,000 SNPs); the software program Beagle was used to generate a uniform set of makers across both platforms (~1.8 million SNPs). GWAS was performed using a mixed linear regression model that included a random polygenic term determined from a genomic relationship matrix calculated from select trait associated SNPs, random herd effect, and fixed covariates sex and age. Significant loci were identified for several EMS traits. Specific examples include loci on ECA1 (P = 5.04e-08) and ECA15 (P = 5.43e-12) for fasting adiponectin and triglyceride levels, respectively. For fasting insulin levels, significant loci were identified on ECA18 (P = 4.77e-10) and ECA6 (P = 4.33e-09). Candidate genes in these regions include a gene associated with obesity in humans on ECA18, and a gene associated with height and insulin resistance on ECA6. Future directions include haplotype analysis and interrogation of these regions through whole genome sequencing. Hyperphosphatemia, hypocalcemia, increased parathyroid hormone (PTH), and reduced vitamin D metabolite concentrations were recently documented in critically ill foals by our group. However, information on fibroblast growth factor-23 (FGF-23) and klotho, two factors that regulate vitamin D activation and PTH secretion, and their association with calcium, phosphorus, PTH, and vitamin D concentrations in healthy and hospitalized foals is lacking. FGF-23 is released by osteocytes in response to increased 1,25(OH) 2 D 3 , PTH, and phosphorus concentrations. FGF-23 suppresses renal 1a-hydroxylase activity and PTH synthesis. Klotho is secreted by the kidneys and acts as a co-receptor for FGF-23. The goal of this study was to determine the relevance of FGF-23 and klotho in calcium, phosphorus, PTH, and vitamin D regulation, including their association with clinical and laboratorial findings, disease severity and outcome in hospitalized foals. We hypothesized that elevated FGF-23 and reduced klotho concentrations will be frequent, associated with calcium and phosphorus dysregulation, PTH and vitamin D metabolite (25(OH)D 3 , 1,25(OH) 2 D 3 ) concentrations, severity of illness, and mortality in critically ill foals.