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, 8 (9), e74372
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Dogs and Humans Share a Common Susceptibility Gene SRBD1 for Glaucoma Risk

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

Nobuyuki Kanemaki et al. PLoS One.

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.

Conflict of interest statement

Competing Interests: Two of the authors, KTT and MI are employed by the Menicon Co., Ltd. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Linkage disequilibrium (LD) plot of five SNPs of the SRBD1 gene.
A) LD structure in Shiba-Inus. B) LD structure in Shih-Tzus. The D’ value and r2 value (in parentheses) corresponding to each SNP pair are expressed as a percentage and shown within the respective square. The color scheme is based on D' and LOD score values: bright red (LOD ≥2 and D' = 1); shades of pink/red (LOD ≥2 and D' <1); blue (LOD <2 and D' = 1); white (LOD <2 and D' <1).

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Grant support

This study was supported by the MEXT-Supported Program for the Strategic Research Foundation at Private Universities. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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