title: Dog MHC alleles containing the human RA shared epitope confer susceptibility to canine rheumatoid arthritis.
abstract: To determine whether canine rheumatoid arthritis (CRA) is associated with dog MHC (DLA-DRB1) alleles which contain the QRRAA/RKRAA conserved third hypervariable region (3HVR) sequence, DNA samples were extracted from 61 dogs with clinically diagnosed small-joint polyarthritis and from 425 controls. Breed-matched controls were available for 41 cases. DLA-DRB1 genotypes were identified using molecular typing methods. Phenotype frequencies were compared between cases and controls and odds ratios with 95% confidence intervals calculated. Several DLA-DRB1 alleles were associated with increased risk for CRA: DLA-DRB1*002, DRB1*009, and DRB1*018. This was also observed for the presence of any shared epitope (SE)-bearing allele. The associations with DLA-DRB1*002 and the SE were maintained when only breed-matched cases and controls were compared. This study suggests that a conserved amino acid motif in the 3HVR present in some DRB1 alleles of both dogs and humans is associated with rheumatoid arthritis in both species.
authors.affiliation: Mammalian Immunogenetics Research Group, Faculty of Veterinary Medicine, University of Liverpool, L69 3BX, UK. bill@fs1.ser.man.ac.uk
authors.forename: W E
authors.initials: WE
authors.lastname: Ollier
authors.forename: L J
authors.initials: LJ
authors.lastname: Kennedy
authors.forename: W
authors.initials: W
authors.lastname: Thomson
authors.forename: A N
authors.initials: AN
authors.lastname: Barnes
authors.forename: S C
authors.initials: SC
authors.lastname: Bell
authors.forename: D
authors.initials: D
authors.lastname: Bennett
authors.forename: J M
authors.initials: JM
authors.lastname: Angles
authors.forename: J F
authors.initials: JF
authors.lastname: Innes
authors.forename: S D
authors.initials: SD
authors.lastname: Carter
mesh_terms: D000483:Alleles; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology / Q000662:veterinary*; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000235:genetics; D004285:Dogs; D000939:Epitopes / Q000737:chemistry / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008969:Molecular Sequence Data; D016017:Odds Ratio; D017385:Sequence Homology
chemical_list: D022801:Complementarity Determining Regions; D000939:Epitopes