Polymerase chain reaction-based genotyping for allotypic markers of immunoglobulin kappa shows allelic association of Km with kappa variable segment

Abstract Allotypic markers of immunoglobulin kappa (Km) may be determined using a novel method of amplification of the constant segment (C K ) (IGKC) by polymerase chain reaction (PCR) followed by restriction enzyme digestion. Restriction sites in the C K PCR product correlate with allotypic differences among Km(1), Km(1,2), and Km(3) alleles. An Acc I site in the PCR product correlates with Km(3); and presence or absence of a Mae II site correlates with the Km(1) or Km(1,2) allele, respectively. Km allelic frequencies were determined in a Caucasian population and compared to genotypic frequencies of nearby polymorphic markers. Among unrelated individuals with rheumatoid arthritis (RA) and controls, there is no evidence of allelic association between CD8A and polymorphic markers of the immunoglobulin kappa region [a V K (IGKV) Bgl II polymorphism about 24 kb centromeric to C K , Km allotype, and a Sac I polymorphism 3.5 kb telomeric to the C K segment]. Similarly, there is no allelic association of the Sac I C K polymorphism with Km or with the Bgl II V K polymorphism. However, there is evidence of allelic association of V K B3 and Km, specifically between the V K Bgl II 2.2-kb allele and Km(3) and also between the V K 3.5-kb allele and Km(1,2). Therefore, Km typing by PCR-based methods suggests the presence of allelic association between polymorphisms within the coding region of the C K segment and the nearest V K segment.