title: Dogs and humans share a common susceptibility gene SRBD1 for glaucoma risk.
abstract: 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.
authors.affiliation: Veterinary Teaching Hospital, Azabu University, Sagamihara, Kanagawa, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kanemaki
authors.forename: Kissaou T
authors.initials: KT
authors.lastname: Tchedre
authors.forename: Masaki
authors.initials: M
authors.lastname: Imayasu
authors.forename: Shinpei
authors.initials: S
authors.lastname: Kawarai
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yoshino
authors.forename: Norihiko
authors.initials: N
authors.lastname: Itoh
authors.forename: Akira
authors.initials: A
authors.lastname: Meguro
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Mizuki
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000071096:ADAMTS Proteins; D000123:Acetyltransferases / Q000235:genetics*; D000483:Alleles; D000818:Animals; D004285:Dogs; D000081031:Fatty Acid Elongases; D005260:Female; D020022:Genetic Predisposition to Disease; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007429:Intraocular Pressure; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins / Q000235:genetics*; D012307:Risk Factors; D014065:Tonometry, Ocular
chemical_list: C000630954:ELOVL5 protein, human; D016601:RNA-Binding Proteins; C000588682:SRBD1 protein, human; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases; D051722:ADAM Proteins; D000071096:ADAMTS Proteins; C494614:ADAMTS10 protein, human
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