GENETIC-POLYMORPHISM OF THE 4TH COMPONENT OF HUMAN-COMPLEMENT - POPULATION STUDY AND PROPOSAL FOR A REVISED NOMENCLATURE BASED ON GENOMIC PCR TYPING OF RODGERS AND CHIDO DETERMINANTS

The fourth component of human complement (C4) is coded for by two homo logous genes, C4A and C4B, located in the class III region of the majo r histocompatibility complex (MHC). Genetic typing of C4A and B allele s is routinely carried out by high-voltage agarose gel electrophoresis . The electrophoretic C4 polymorphism can be further subdivided by the Rodgers (Rg) and Chido (Ch) blood groups, which are antigenic determi nants of the C4A and B alpha-chains, respectively. We have used a rece ntly described direct PCR typing method using sequence-specific primer s (PCR-SSP) in combination with electrophoretic C4 typing as well as g enomic RFLP analysis to determine the frequency of C4 allotypes, Rg/Ch subtypes and C4A-B haplotypes in a family study of the German populat ion. As the current C4 allele designation does not provide any informa tion about the presence or absence of Rodgers and Chido antigens, we h ave developed an extension to the existing C4 nomenclature. This revis ed allele designation combines the existing numerical allotypes define d by electrophoretic mobility with eight subtypes (01-08) based on Rg/ Ch PCR genotyping results. Using this approach, most electrophoretic a llotypes could be subdivided. Among the C4A allotypes, the most common allele was A0301 (59.9%), and the most common subtype among all elec trophoretic allotypes was 01 (85.1%; = Rg1,2-positive, Ch-negative). F or C4B, the most common allele was B0101 (64.3%), and the most common subtype was 01 (79.6%; = Ch1,2,3,4,5,6-positive, Rg-negative). The su btypes 03, 04, 07 and 08 of the C4A allotypes, and the subtypes 03, 07 and 08 of the C4B allotypes, were not detected in this study. The ana lysis of duplicated C4 alleles revealed considerable heterogeneity of their subtypes. The results demonstrate that all known C4 allotypes ca n now be assigned unambiguously, which facilitates the identification of MHC haplotypes relevant for transplantation and disease association studies.