Veterinary Teaching Hospital, Azabu University, Sagamihara, Kanagawa, Japan.
PLoS One. 2013 Sep 11;8(9):e74372. doi: 10.1371/journal.pone.0074372. eCollection 2013.
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.
青光眼是一种与眼内压升高相关的退行性视神经病变。原发性开角型青光眼是犬类最常见的青光眼类型，在柴犬和西施犬中发病率最高。这些品种的犬种已知具有异常的虹膜角膜角和发育不良的前睫状韧带。然而，这些犬的遗传和基因背景尚未阐明。在这项研究中，我们调查了青光眼候选基因 SRBD1、ELOVL5 和 ADAMTS10 的多态性与柴犬和西施犬青光眼之间的关联。我们使用直接 DNA 测序分析了这三个基因中的 11 个多态性。三个 SRBD1 SNP(rs8655283、rs22018514 和 rs22018513)与柴犬的青光眼显著相关，而外显子 4 中的同义 SNP(rs22018513)显示出最强的关联(P=0.00039，OR=3.03)。条件分析表明，rs22018513 可以解释这些 SNP 与柴犬青光眼关联的大部分原因。在西施犬中，只有 SRBD1 内含子 1 中的 rs9172407 与青光眼显著相关(P=0.0014，OR=5.25)。ELOVL5 或 ADAMTS10 多态性与柴犬和西施犬的青光眼之间没有显著关联。结果表明，SRBD1 多态性在柴犬和西施犬的青光眼发病机制中起重要作用。SRBD1 多态性也与人类的正常眼压性和高眼压性青光眼有关。因此，SRBD1 可能是人类和犬类青光眼的共同易感基因。我们预计，本研究的核苷酸测序数据可用于遗传测试，首次以高精度确定犬类青光眼的遗传状况和易感性。此外，由 SRBD1 多态性引起的犬类青光眼可能是研究人类青光眼的有用动物模型。
