G Moxley1. 1. Division of Rheumatology, Allergy and Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
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 (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.
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.
Authors: B Mulcahy; F Waldron-Lynch; M F McDermott; C Adams; C I Amos; D K Zhu; R H Ward; D O Clegg; F Shanahan; M G Molloy; F O'Gara Journal: Am J Hum Genet Date: 1996-09 Impact factor: 11.025