A genetic investigation of equine recurrent uveitis in the Icelandic horse breed

Abstract

Summary Equine recurrent uveitis (ERU) is an autoimmune disease defined by inflammation of the uveal tract of the eye. The cause of ERU is thought to be complex, involving both genetic and environmental factors. The purpose of this study was to investigate potential genetic risk factors for ERU in the Icelandic horse. Fifty‐six Icelandic horses (11 affected with ERU and 45 controls) living in Denmark and the USA, eight years or older, were included in the study. A case–control GWAS was performed using the GGP Equine 80K array on the Illumina Infinium HD Beadchip using 40 horses. A mixed linear model analysis identified a single SNP on ECA 11 (BIEC2_141650; NC_009154.3:g.3817009A>G) that reached genome‐wide significance (p = 1.79 × 10−7). This variant was within an intron of tissue inhibitor of metalloproteinase 2 (TIMP2), a gene previously implicated in ERU. Sanger sequencing identified a single coding variant in this gene; however it was a synonymous mutation (NC_009154.3:g.3858193C>T) and was not perfectly concordant with ERU phenotype (p = 0.68). Further investigation of TIMP2 is warranted. Additional horses and markers are needed to identify other potential loci worthy of further investigation as contributors to ERU risk in Icelandic horses.

A review of investigated risk factors for developing equine recurrent uveitis

“…Additional investigations are needed to determine the relative risk of these two classifications of ERU among Icelandic horses. A genome‐wide association study using the same population of Icelandic horses identified an association on ECA 11, but no causal genetic risk factors have been identified at this time 107 . Additional investigations are needed to replicate these findings and identify potential variants for further investigations to understand the role of genetics in the onset of ERU among Icelandic horses.…”

“…Breed predisposition provides evidence of a genetic component for the development of ERU. For example, classic ERU has been recognized to occur more commonly among warmblood and Icelandic horses, although limited information about prevalence of the classic subtype is available for these breeds 9,107 . For posterior ERU, previous investigations identified an overrepresentation of warmblood horses among ERU cases, but limited information is available about the propensity or relative risk for developing posterior uveitis for any one breed 4,7 …”

Preliminary evaluation of safety and migration of immune activated mesenchymal stromal cells administered by subconjunctival injection for equine recurrent uveitis

“…The inciting causes for development of ERU are likely multifactorial and remain unclear in many cases, but may involve genetic predisposition in certain breeds (e.g., Appaloosas, Warmbloods, Icelandics) or infection with Leptospira spp. (5, [9][10][11][12]. Current treatments for ERU include a combination of topical and systemic anti-inflammatories, atropine, antibiotics (if active Leptospira spp.…”