Immunoglobulin kappa genotype confers risk of rheumatoid arthritis among hla–dr4 negative individuals

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Abstract
Because DNA polymorphisms of immunoglobulin kappa confer risk for rheumatoid arthritis (RA) and not all persons with RA have the HLA–DR4 marker, genomic polymorphisms of immunoglobulin kappa and HLA–DRβ were determined in white patients with RA. Compared with control subjects matched for DRβ genotype, the homozygous genotype of the constant segment of immunoglobulin kappa (Cκ) was more frequent in the subgroups of RA patients without the DRβ genotype corresponding to HLA–DR4 (relative risk 6.2, P < 0.01) and patients without DR4 or DR1 (relative risk 6.7, P = 0.013), but not in the DR4+ RA subgroup. Therefore, RA may be a genetically heterogeneous disease, with HLA–DR4 marking one genetic subset and the homozygous Cκ genotype marking another.