Both inherited HLA-haplotypes are important in the predisposition to rheumatoid arthritis

The distribution of the HLA-DR allele frequencies of 105 RA patients has been compared with the expected distribution under recessive and dominant modes of inheritance using control data from 2041 controls and the antigen genotype frequency among patients methodology. The observed distribution was compatible with a recessive mode of HLA-linked inheritance in RA, with a dominant mode rejected, whether HLA-DR4 was considered alone, or HLA-DR4 and HLA-DR1 were combined as if they were behaving as a single predisposing gene. Mean sibship concordance rates (MSCRs) were calculated for categories of proband HLA-DR genotypes. The highest MSCR was for HLA-DR4 homozygous probands, and the lowest for HLA-DR2 or 7/non-4 genotypes. These combined observations suggest that interactions between both inherited HLA-haplotypes are important in the predisposition to RA.