Genetics and epidemiology of hypothyroidism and symmetrical onychomadesis in the Gordon setter and the English setter.

Background: 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.

Results: 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-DQB1*00201 (OR = 3.6, 95 % CI: 2.1-6.4, p < 0.001) and DLA-DQA1*00101 (OR = 2.9, 95 % CI: 1.3-6.6, p < 0.001), respectively. In the Gordon setter, the haplotype DLA-DRB1*01801/DQA1*00101/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).

Conclusion: 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.