Equine Recurrent Uveitis Risk and Severity (ERUR / ERUS)
Gene or Region: ECA20 (IL17A and IL17F)
Reference Variant: A
Mutant Variant: G
Affected Breeds: Many
Research Confidence: Preliminary - Strong correlation in early studies, results have only been shown correlation in early studies of Warmblood population
Explanation of Results: ERUR/ERUR = homozygous for Equine Recurrent Uveitis Risk, increased risk ERUR/n = heterozygous for Equie Recurrent Uveitis Risk, possible increased risk n/n = no variant detected ERUS/ERUS = homozygous for Equine Recurrent Uveitis Severity, increased severity of symptoms ERUS/n = heterozygous for Equie Recurrent Uveitis Risk, possible increased severity / carrier n/n = no variant detected, normal severity
General Information
Equine Recurrent Uveitis (ERU) is the most common cause of blindness in horses. It is thought to affect 3-15% of the horse population worldwide. With multiple causes, Equine Recurrent Uveitis in horses may originate from environmental factors, ocular infection of Leptospira, a genetic predisposition or a combination of these factors. Characterized by episodes of inflammation of the middle layer of the eye, ERU leads to the development of cataracts, glaucoma and eventually complete loss of vision.
Appaloosas, European Warmbloods, draught breeds and Standardbred trotters are most commonly affected by ERU. Foreseeably, these diverse breeds present different modes of genetic inheritance for ERU. For example, in Appaloosa horses a Single Nucleotide Polymorphism (SNP) located on TRPM1 (the same gene responsible for the characteristic spotting of the breed) indicates a higher chance of disease development. Additionally, certain mutations within the MHC region of the genome, which encompasses genes regulating immune response, indicate disease severity.
In a population of German Warmbloods, a SNP on ECA 20 located near interleukin genes IL-17A and IL-17F proved significant in predicting horses affected by ERU. The “G” allele, rather than the more common allele “A”, showed a strong correlation with ERU. Horses with two copies of the "G" mutation are 80% more likely to be affected by ERU while those with only one allele (A/G) are thought to be at relatively moderate increased risk, but are "carriers" and can transmit this “G” risk allele to their offspring.
A second SNP on ECA 18 located within an intron of PLEKHM3 and downstream of CRYGA-CRYGF, significantly correlated to ERU severity. A mutation from G to A increased the severity of disease in 69% to 78% of the cases.
Thus a horse inheriting two copies in this region (A/A) was shown to be associated to be at increased symptom severity should they acquire ERU via infection or otherwise (independent of genetic "risk" for any heritable form of ERU). Studies indicate that horses with two copies of the "A" mutation are likely to suffer more severe symptoms than the average horse with the same disease. Horses with only one allele (A/G) are thought to be at moderately increased risk & carriers due to their ability to produce affected offspring.
References
Witkowski L, Cywinska A, Paschalis-Trela K, Crisman M, Kita J. (2015) Multiple etiologies of equine recurrent uveitis--A natural model for human autoimmune uveitis: A brief review. Comp Immunol Microbiol Infect Dis. 2016 Feb;44:14-20
Kulbrock M, Lehner S, Metzger J, Ohnesorge B, Distl O (2013) A Genome-Wide Association Study Identifies Risk Loci to Equine Recurrent Uveitis in German Warmblood Horses. PLoS ONE 8(8): e71619. doi:10.1371/journal.pone.0071619
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