Genetic polymorphism of the complement C2 in Japanese

Area of Science:

• Immunogenetics
• Human Complement System

Background:

• The second component of human complement (C2) plays a crucial role in both classical and lectin complement pathways.
• Genetic variations in complement components can influence immune responses and disease susceptibility.
• Previous studies have indicated population-specific genetic polymorphisms in complement proteins.

Purpose of the Study:

• To investigate the genetic polymorphism of the second component of human complement (C2) in a healthy adult Japanese population.
• To identify and characterize novel C2 phenotypes and alleles.
• To examine the linkage disequilibrium between C2 and Human Leukocyte Antigen (HLA) loci and assess C2 hemolytic activity.

Main Methods:

• Isoelectric focusing in polyacrylamide gel electrophoresis (IEF-PAGE) was used to separate C2 protein variants.
• A specific hemolytic overlay method was employed for C2 phenotyping.
• HLA-A, -B, and -C typing was performed using standard serological methods.
• C2 hemolytic activities of different phenotypes were assayed.

Main Results:

• Besides previously known C2 phenotypes (C, AC, BC), a rare double-banded phenotype (A'C) was observed, along with homozygous variant (A) and heterozygous variant (AB).
• Allele frequencies were estimated: C2c (0.939), C2A (0.034), C2B (0.022), and C2A' (0.006).
• Significant associations were found between C2A and HLA-B15/A26, and C2B and HLA-Bw61, indicating population-specific linkage disequilibrium patterns between C2 and HLA loci, with C2 showing closer linkage to HLA-B than HLA-A.

Conclusions:

• The study identified novel C2 genetic variants in the Japanese population and confirmed population-specific linkage disequilibrium between C2 and HLA loci.
• The findings suggest that the C2 structural locus is more closely linked to HLA-B than HLA-A in Japanese individuals.
• Differences in C2-HLA associations between Japanese and Caucasian populations were highlighted, underscoring the importance of population-specific genetic studies in immunogenetics.