Variable‐Constant Segment Genotype of Immunoglobulin Kappa is Associated with Increased Risk for Rheumatoid Arthritis

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Abstract
Objective. To further investigate the association of rheumatoid arthritis (RA) with a particular genotype identified by a restriction site polymorphism near the constant segment of immunoglobulin kappa (Ck). Methods. The frequencies of genomic DNA polymorphisms detected within or near Ck (the most Ck‐proximal variable segment [Vk] B3 and a T lymphocyte marker [CD8A]) were determined by Southern blotting and hybridization. The frequencies of coding‐region polymorphisms of Ck (Km allotypes) were determined by amplification by polymerase chain reaction followed by restriction enzyme digestion. Results. Although the frequencies of B3, Km, and CD8A genotypes were not different between RA and normal control populations, more individuals were homozygous for both Ck and B3 in the RA group (relative risk 2.2, P < 0.01), especially in the DR4‐negative RA subgroup (relative risk 3.9, P < 0.001). Conclusion. The homozygous genotype of an approximately 30,000‐base region including the Ck segment confers an elevated risk for RA, particularly in the DR4‐negative subgroup.