Dog MHC alleles containing the human RA shared epitope confer susceptibility to canine rheumatoid arthritis.
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.
Ollier
W E
WE
Mammalian Immunogenetics Research Group, Faculty of Veterinary Medicine, University of Liverpool, L69 3BX, UK. bill@fs1.ser.man.ac.uk
Kennedy
L J
LJ
Thomson
W
W
Barnes
A N
AN
Bell
S C
SC
Bennett
D
D
Angles
J M
JM
Innes
J F
JF
Carter
S D
SD
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
D022801:Complementarity Determining Regions; D000939:Epitopes