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Variable-constant segment genotype of immunoglobulin kappa is associated with increased risk for rheumatoid arthritis
1Division of Rheumatology, Allergy and Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
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 (C kappa).
Methods:
The frequencies of genomic DNA polymorphisms detected within or near C kappa (the most C kappa-proximal variable segment [V kappa] B3 and a T lymphocyte marker [CD8A]) were determined by Southern blotting and hybridization. The frequencies of coding-region polymorphisms of C kappa (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 C kappa and B3 in the RA group (relative risk 2.2, P less than 0.01), especially in the DR4-negative RA subgroup (relative risk 3.9, P less than 0.001).
Conclusion:
The homozygous genotype of an approximately 30,000-base region including the C kappa segment confers an elevated risk for RA, particularly in the DR4-negative subgroup.