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Glaucoma is a degenerative optic neuropathy that is associated with elevated intraocular pressure. Primary open angle glaucoma is the most common type of glaucoma in canines, and its highest incidence among dog breeds has been reported in Shiba-Inus, followed by Shih-Tzus. These breeds are known to have an abnormal iridocorneal angle and dysplastic prectinate ligament. However, the hereditary and genetic backgrounds of these dogs have not yet been clarified. In this study, we investigated the association between polymorphisms of the glaucoma candidate genes,  SRBD1 ,  ELOVL5 , and  ADAMTS10 , and glaucoma in Shiba-Inus and Shih-Tzus. We analyzed 11 polymorphisms in these three genes using direct DNA sequencing. Three  SRBD1  SNPs, rs8655283, rs22018514 and rs22018513 were significantly associated with glaucoma in Shiba-Inus, while rs22018513, a synonymous SNP in exon 4, showed the strongest association ( P =  0.00039, OR = 3.03). Conditional analysis revealed that rs22018513 could account for most of the association of these SNPs with glaucoma in Shiba-Inus. In Shih-Tzus, only rs9172407 in the  SRBD1  intron 1 was significantly associated with glaucoma ( P =  0.0014, OR = 5.25). There were no significant associations between the  ELOVL5  or  ADAMTS10  polymorphisms and glaucoma in Shiba-Inus and Shih-Tzus. The results showed that  SRBD1  polymorphisms play an important role in glaucoma pathology in both Shiba-Inus and Shih-Tzus.  SRBD1  polymorphisms have also been associated with normal- and high-tension glaucomas in humans. Therefore,  SRBD1  may be a common susceptibility gene for glaucoma in humans and dogs. We anticipate that the nucleotide sequencing data from this study can be used in genetic testing to determine for the first time, the genetic status and susceptibility of glaucoma in dogs, with high precision. Moreover, canine glaucoma resulting from  SRBD1  polymorphisms could be a useful animal model to study human glaucoma.

Dogs and Humans Share a Common Susceptibility Gene SRBD1 for Glaucoma Risk