Human MHC class III genes, BF and C4. Polymorphism, complotypes and HLA class I and II associations in the Lombardy population (Italy).

The polymorphisms of the fourth component of human serum complement and factor B (BF) (controlled by class III MHC genes) was investigated in a panel of 250 unrelated individuals from the Lombardy population, previously HLA typed (A, B, C, DR, DQ antigens) and in 25 families. Nine different alleles at the C4A and eight at the C4B loci were detected. At both loci, alleles without a gene product (i.e. "null alleles") were observed with high frequency: 8.2% for C4A "nulL" and 10% C4B "null". As expected from allele frequencies the most common haplotype was C4A*3, C4B*1 (52%). The most common BF alleles, BF*S and BF*F had a frequency of 77.7% and 17.7% respectively, while the gene frequencies of SO.7 and F1 were 2.9 and 0.9% respectively. The association of complotypes and HLA haplotypes was analysed in 50 chromosomes. The most common combination, defined by class I, II and III alleles was B35-S31-DR5 (11%) followed by B16(38)-S31-DR5 with a frequency of 6.5%. Two duplications at the C4B locus were detected. A new variant (C4A*X) strikingly faster than that of the C4A*6 product was identified in two related individuals (aunt and nephew). The practical advantages of complotype determination in disease association studies and in healthy population is discussed.