An investigation of the C4 gene arrangement in ethnic Chinese (Taiwanese)

Abstract

C4 complement components are encoded by two genes, C4A and C4B , located on chromosome 6p21.3 of the major histocompatibility complex class III region. The isotypic residues at position 1101-1106 of the C4A gene contain the Pro-Cys-Pro-Val-Leu-Asp sequence which has a higher affinity for binding amino group-containing antigens, while C4B contains the Leu-Ser-Pro-Val-Ileu-His sequence which has a higher affinity for hydroxyl group-containing antigens. These two genes show different reaction rates which infer solubilization of antibody-antigen aggregates and propagation of the activation pathway to form the membrane attack complex. Using a polymerase chain reaction-based amplification method to identify and differentiate the locations of the C4A and C4B genes adjacent to the respective CYP21A2P and CYP21A2 genes, the isotypic residues at position 1101-1106 for the C4 isotype were categorized into five haplotypes of C4 gene arrangements. Among them, we found that 65% of the gene proportions between C4A and C4B were balanced, while 35% of them were unbalanced in this ethnic Chinese (i.e. Taiwanese) cohort. We consider that the unbalanced arrangements of the C4 locus in the individuals might have influenced the clearance of apoptotic debris and immune complexes which may injure tissue by initiating autoimmune diseases and immunity responses associated with susceptibility to viral and bacterial infections.