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Canine chronic superficial keratitis (CSK) is an inflammatory corneal disease that leads to blindness if not treated. CSK occurs most frequently in the German Shepherd dog (GSDs). While the normal central cornea has little MHC class II expression, aberrant expression occurs in CSK, associated with secretion of gamma interferon by infiltrating CD4 expressing lymphocytes. Several evidences lend support to the hypothesis that CSK is an immune-mediated disease. Accordingly, to investigate the molecular genetic factors that may be associated to CSK development: 3 STRs (short tandem repeats) linked to DLA (Dog Leukocyte Antigen) class II region (FH2202, FH2054 y FH2975, upstream regulatory regions (URR) and ARS (exon 2) of DLA class II DLA-DRB1, DLA-DQA1 and DLADQB1 genes were genotyped in 73 dogs, including 43 CSK animals. Association was observed in all types of markers, allele FH2054*172 (p value =0.02) and FH2975*320 (p value = 0.005) were associated with a higher risk to develop CKS. The URR-DQB*TATC haplotype was significantly associated with CSK (p = 0.006), increasing almost three folds the risk to develop this disease (OR= 2.87, 95%, CI = 1.4381). Furthermore, the haplotype DRB1*00101/DQA1*00101/DQB1*00201 was associated with a low risk to develop CSK (p=0.02, OR= 0.2, 95%, CI = 0.070.81). Although, the haplotype conformed by promoter and exon 2 of DLA-DQB1 URR-DQB*TATC/*01302 was significant associated with CSK (p=0.003, OR= 4.56, 95%, CI = 1.7416.53) increasing five folds the risk to develop the disease. This study confirms the role of MHC class II in the development of CSK and provides new data about the local population of GSD. This genetic association also supports the previous clinical, histological and pharmacological studies of CSK as an immune-mediated disease and could potentially be used to identify susceptibly animals that require monitoring for early pathological changes to reduce blindness and to ameliorate reproductive management.

Estudio de asociación mediante marcadores genéticos de la queratitis superficial crónica en perros de raza ovejero alemán