FCGR3 variants and expression of human neutrophil antigen-1a, -1b, and -1c in the populations of northern Germany and Uganda.

BACKGROUND

Human neutrophil antigen-1c (HNA-1c) (SH) has been described as the third alloantigen of the Fc receptor type IIIb (FcgammaRIIIb) for IgG beside the known alloantigens HNA-1a (NA1) and HNA-1b (NA2). Controversy exists on the assignment of the HNA-1c coding gene to the FCGR3B locus and on a possible linkage between the HNA-1c and HNA-1a coding genes.

STUDY DESIGN AND METHODS

Two hundred sixty northern German blood donors and 43 individuals from Uganda were typed for FCGR3B1 (NA1), FCGR3B2 (NA2), and FCGR3B3 (SH) by allele-specific PCR. In a subset of FCGR3B3-positive probands, PCR-amplified FCGR3 fragments were subcloned and sequenced. Transmission of FCGR3B*3 was analyzed in family studies. A possible correlation with the FcgammaRIIIb alloantigen expression was investigated by flow cytometry.

RESULTS

In the northern German population, FCGR3B3 was found exclusively in individuals carrying FCGR3B1 independent of the existence of FCGR3B2 at a frequency of 5 percent. In the individuals from Uganda, each possible combination of FCGR3B1, FCGR3B2, and FCGR3B3 was detected. FCGR3B*3 frequency was 34.9 percent. Within both populations, some individuals carried each of the three genotypes. DNA sequencing revealed new FCGR3 variants caused by single nucleotide exchanges at the typical polymorphic positions. In one individual, six different FCGR3 variants were detected.

CONCLUSION

The coincidence of the three known FCGR3B alleles varies within the population of Germany and Uganda. Three simultaneous FCGR3B forms may be explained by two gene loci, but the basis of the high number of different variants in some individuals still remains unclear. Possible explanations may be a hypermutation mechanism or a number of FCGR3 higher than expected hitherto.