Variable-constant segment genotype of immunoglobulin kappa is associated with increased risk for rheumatoid arthritis.
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).


CONCLUSIONS
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.
Moxley
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Division of Rheumatology, Allergy and Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics; D004247:DNA / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors
D016827:CD8 Antigens; D006684:HLA-DR Antigens; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D004247:DNA