Genetic polymorphism of human complement C4 and detection of heterozygotes

• Published in: Nature (London) 1979-11, Vol.282 (5735), p.205-207
• Main Authors: Awdeh, Z. L, Raum, D, Alper, C. A
• Format: Article
• Language: English
• Subjects: Complement C4 - genetics; Genotype; Heterozygote; Humanities and Social Sciences; Humans; letter; multidisciplinary; Pedigree; Polymorphism, Genetic; Science; Science (multidisciplinary)
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/282205a0

Many components of complement exhibit inherited structural polymorphism, with at least two alleles being common in one or more of the major races of man 1–9 . However, definition of genetic polymorphism in human C4 has proved a difficult task. Differences between the electrophoretic patterns of C4 in EDTA plasma from different individuals were detected by Rosenfeld and co-workers 10,11 , but these differences could not be explained by any simple genetic model. O'Neill and co-workers 12 , using a system similar to that of a previous study 13 , interpreted the electrophoretic patterns in a completely different way from previous workers 13,14 , stating that there were three: F, FS and S. They also found that C4 F carried Rodgers or Rg(a + ) serologie reactivity and C4 S carried Chido or Ch(a + ) reactivity 15 . These ‘blood group’ antigens had previously been shown to be closely linked to HLA 16,17 . O'Neill proposed 15 that C4 is genetically controlled by two closely linked loci, one for C4 F and one for C4 S, and postulated that deficiency states for one or the other locus are common but rarely occur together. The sets of haplotypes were postulated to be C4Fs ° (or C4F ), C4f ° S (or C4S ) and C4FS . In this model, the C4 F individuals are Rg(a +)Ch(a −), C4 S individuals are Rg(a −)Ch(a +) and C4 FS persons are Rg(a +)Ch(a +). The chief problem with the methods of typing, both electrophoretic and serologie, is that C4Fs ° and C4f ° S can usually only be detected in the homozygous state, thus severely limiting their usefulness. We have now developed a method of C4 typing that allows detection of C4Fs ° and C4f ° S in heterozygotes, and permits the study of genetic polymorphism of C4 in the general population. Our observations confirm and extend the two-locus genetic model of O'Neill and coworkers.