Complement C4 Protein and DNA Typing Methods

Complement C4 is the only component coded for by two nearly identical isotypic genes, C4A and C4B. The C4 genes are located tandemly arranged each with a steroid 21-hydroxylase (CYP21) gene at its 3′ end, together with the genes for C2 and factor B in the major histocompatibility complex (MHC) class III gene region between HLA-B and human leukocyte antigen (HLA)-DR (1 ). C4 polymorphism can be defined at three levels: (i) at the genomic level regarding the gene structure and the number of C4 genes; (ii) at the DNA sequence level by determining variability in the coding sequence, as well as by analyzing restriction fragment length polymorphisms (RFLPs) in introns and flanking regions; (iii) at the protein level by electrophoretic and serological methods to distinguish C4 isotypes and allotypes.