Ziener Martine Lund, Dahlgren Stina, Thoresen Stein Istre, Lingaas Frode
Department of Basic Sciences and Aquatic Medicine, Norwegian University of Life Sciences, Oslo, Norway ; Fredrikstad Animal Hospital, Fredrikstad, Norway.
Department of Basic Sciences and Aquatic Medicine, Norwegian University of Life Sciences, Oslo, Norway.
Canine Genet Epidemiol. 2015 Aug 21;2:12. doi: 10.1186/s40575-015-0025-6. eCollection 2015.
Hypothyroidism is one of the most common endocrine disorders, whereas symmetrical onychomadesis is a rare claw disease in the general dog population. The aims of this study were to estimate the prevalence of hypothyroidism and symmetrical onychomadesis in a birth cohort of 291 Gordon setters at eight years of age. Further, to describe the age at diagnosis of hypothyroidism in the 68 Gordon setters and 51 English setters included in the DLA study. Finally, to elucidate potential associations between dog leukocyte antigen (DLA) class II and hypothyroidism and/or symmetrical onychomadesis in the Gordon setter and the English setter.
In the birth cohort of eight years old Gordon setters, 2.7 % had hypothyroidism and 8.9 % had symmetrical onychomadesis, but only one out of these 291 dogs (0.3 %) had both diseases. Mean age at diagnosis of hypothyroidism for dogs included in the DLA study was 6.4 years (95 % CI: 5.6-7.2 years) in the Gordon setters and 7.7 years (95 % CI: 7.2-8.2 years) in the English setters. The DLA alleles most associated with hypothyroidism in the Gordon setter and English setter were DLA-DQB100201 (OR = 3.6, 95 % CI: 2.1-6.4, p < 0.001) and DLA-DQA100101 (OR = 2.9, 95 % CI: 1.3-6.6, p < 0.001), respectively. In the Gordon setter, the haplotype DLA-DRB101801/DQA100101/DQB1*00802 was significantly associated with both symmetrical onychomadesis (OR = 2.9, 95 % CI: 1.7-5.2, p < 0.001) and with protection against hypothyroidism (OR = 0.3, 95 % CI: 0.2-0.5, p < 0.001).
Hypothyroidism is a complex disease where DLA genes together with other genes may be involved in the pathogenesis of the disease. In the Gordon setter, one DLA haplotype that was associated with protection against hypothyroidism was also associated with symmetrical onychomadesis. These findings indicate that closely linked genes, instead of or together with the DLA genes themselves, may be associated with hypothyroidism and symmetrical onychomadesis. In a breed where several autoimmune diseases are prevalent all possible associations between DLA genes and actual diseases need to be investigated before DLA is considered used as a tool for marker-assisted selection.
甲状腺功能减退是最常见的内分泌疾病之一,而对称性甲脱落是普通犬类中一种罕见的爪部疾病。本研究的目的是估计291只戈登雪达犬出生队列在8岁时甲状腺功能减退和对称性甲脱落的患病率。此外,描述参与DLA研究的68只戈登雪达犬和51只英国雪达犬中甲状腺功能减退的诊断年龄。最后,阐明犬白细胞抗原(DLA)II类与戈登雪达犬和英国雪达犬甲状腺功能减退和/或对称性甲脱落之间的潜在关联。
在8岁的戈登雪达犬出生队列中,2.7%患有甲状腺功能减退,8.9%患有对称性甲脱落,但这291只犬中只有1只(0.3%)同时患有这两种疾病。参与DLA研究的犬甲状腺功能减退的诊断平均年龄在戈登雪达犬中为6.4岁(95%CI:5.6 - 7.2岁),在英国雪达犬中为7.7岁(95%CI:7.2 - 8.2岁)。在戈登雪达犬和英国雪达犬中,与甲状腺功能减退最相关的DLA等位基因分别是DLA - DQB100201(OR = 3.6,95%CI:2.1 - 6.4,p < 0.001)和DLA - DQA100101(OR = 2.9,95%CI:1.3 - 6.6,p < 0.001)。在戈登雪达犬中,单倍型DLA - DRB101801/DQA100101/DQB1*00802与对称性甲脱落(OR = 2.9,95%CI:1.7 - 5.2,p < 0.001)和预防甲状腺功能减退(OR = 0.3,95%CI:0.2 - 0.5,p < 0.001)均显著相关。
甲状腺功能减退是一种复杂疾病,其中DLA基因与其他基因可能共同参与疾病的发病机制。在戈登雪达犬中,一个与预防甲状腺功能减退相关的DLA单倍型也与对称性甲脱落相关。这些发现表明,紧密连锁的基因,而非DLA基因本身或与其共同作用,可能与甲状腺功能减退和对称性甲脱落相关。在一个多种自身免疫性疾病普遍存在的品种中,在考虑将DLA用作标记辅助选择工具之前,需要研究DLA基因与实际疾病之间的所有可能关联。