Relative predispositional effects and mode of inheritance of HLA-DRB1 alleles among community-based Caucasian females with rheumatoid arthritis.
Multiple HLA-DRB1 alleles encoding a shared epitope (SE) at amino acid positions 70-74 are associated with susceptibility to rheumatoid arthritis (RA). However, the nature of the association and the mode of inheritance differ depending upon the source of RA patients and laboratory methodology. We studied the relative predispositional effects (RPE) and mode of inheritance of DRB1 alleles among a community-based sample of 180 RA patients and 116 healthy controls, all Caucasian females. Polymerase chain reaction (PCR)-based assays were used for DRB1 genotyping, and the genotypic distributions were analyzed by both the RPE and antigen genotype frequency among patients (AGFAP) methods. We examined the evidence of synergy among DRB1 alleles for RA risk by comparing the observed DRB1 genotype distribution to that predicted under Hardy-Weinberg equilibrium. Fifty-six percent of RA cases were attributable to DRB1 alleles encoding the SE. The RPEs of DRB1 alleles were *0401 > *0404 > *1001 > *0408 > *0101. The strength of the RA association was not significantly different for these alleles. The AGFAP analysis was consistent with a recessive mode of inheritance for DRB alleles, while an additive (dominant) model was rejected. We found no evidence of synergy for RA risk among individual DRB1 alleles based on comparison of the observed vs. predicted genotype distributions. These results suggest that among community-based Caucasian females with RA, the DRB1 RA susceptibility gene influences disease risk in a recessive fashion without synergy among individual DRB1 alleles.
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Department of Medicine, University of Washington, Seattle, USA.
King
M C
MC
Criswell
L A
LA
D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D002140:California; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D044465:White People / Q000235:genetics*
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains