Complement Genetic Feature

Complement Genetic Polymorphism

The complement system is an important part of non clonal or innate immunity that collaborates with acquired immunity to kill pathogens and to facilitate the clearance of immune complexes. The complement is made up of 20 distinct plasma proteins and 9 different membrane proteins. Three components, factor B, C2 and C4 (with 2 isotypes), are coded by polymorphic HLA-linked genes and are sometimes referred to as MHC class III antigens, inherited as compact units called complotypes. The C4 genes are the most polymorphic, including a common null allele (Q0) at both the C4A and C4B loci. Other polymorphic complement factors (not linked to HLA) are C3 (2 common alleles), C6 and C7 (closely linked, with 3 and 2 alleles, respectively). A certain degree of polymorphism has also been described for complement receptors and membrane control proteins. No differences in functional activity are usually detected among different alleles.

Human complement C3 exhibits genetic polymorphism that was first described by Weime and Demeulenaere and Alper and Propp in 1986. The genetic variants of the protein are inherited as autosomal codominant traits and are characterized using prolonged agarose gel electrophoresis of fresh serum. In this way, two common polymorphic forms have been found, designated C3F and C3S. The C3S allele is most common in all races in humans. The C3F allele is relatively frequent in Caucasoids, less common in America Negroes, and extremely rare in Orientals. More than 20 rare allotypes have been characterized by variations in their relative electrophoretic mobilities.

Complement Genetic Feature References

1. Botto M, et al. (1990). Molecular basis of polymorphisms of human complement component C3. The Journal of experimental medicine, 172(4), 1011-1017.
2. Brai M, et al. (1993). Polymorphism of the complement components in human pathology. Annali italiani di medicina interna: organo ufficiale della Societa italiana di medicina interna, 9(3), 167-172.