Haplotype study on C4 polymorphism in Japanese. Associations with MHC alleles, complotypes, and HLA-complement haplotypes.

Genetic polymorphism of the fourth component of human complement (C4) was investigated in 83 Japanese families which have been typed for HLA-A,-B,-C,-DR, C2, and BF. Four common C4A alleles and four common C4B alleles were observed. The allele frequencies estimated from unrelated parents were as follows: C4A3, 0.686; A4, 0.132; A2, 0.106; AQ0, 0.067; ARares, 0.009; C4B1, 0.587; B2, 0.167; B5, 0.088; and BQ0, 0.158. Eight different C4 haplotypes were observed with frequencies of more than 0.01. The estimated haplotype frequencies were as follows: C4A3-B1, 0.513; A4-B2, 0.114; A2-BQ0, 0.106; A3-B5, 0.088; AQ0-B1, 0.059; A3-BQ0, 0.047; A3-B2, 0.038; A4-B1, 0.015; and Rares, 0.021. Strong positive gametic associations were found in the following C4-HLA haplotypes: C4A2BQ0-A24, C4A2BQ0-Bw52, C4A3B5-Bw54, C4A3B5-Bw59, C4A4B2-Bw46, C4A3B5-Cw1, C4A2BQ0-DR2, and C4A3B5-DR4. Eleven complotypes were observed with frequencies of more than 0.01. C4A2BQ0 and C4A3B5 were exclusively associated with BFS-C2C. BFF was associated with C4A3B1. C2AT, C2B, and C2BH were associated with C4A3B1, A4B2, and C4A3B1, respectively. Eight different HLA-complement haplotypes were found to be characteristic of Japanese. These combinations are considerably different from those reported in Caucasoid populations.