Variant FCGR3 genes: transcription and possible origins.

The Fc receptors for human immunoglobulin G (FcgammaR) IIIb are encoded by genes clustered on the long arm of chromosome 1 (band q21 --> 24) and exhibit allelic polymorphisms. Several rare FCGR3B sequences were identified in both white and black donors. However, the origins of these genomic variants are unknown and their transcription has not yet been investigated. Blood from a donor with known FCGR3 variants was used to extract DNA from peripheral blood CD34+ cells, CD19+ B-cells, neutrophils and buccal cells, after which FCGR3 gene sequencing was performed. Additionally, RNA samples from 5 Caucasian individuals containing known variant FCGR3 genes were reverse-transcribed to cDNA and the FCGR3 genes were sequenced. Our results showed that the frequencies of variant clones were higher in B-cell preparations than in CD34+ hematopoietic progenitor cells from peripheral blood and neutrophils. Very high variant frequencies were found in buccal cell-derived clones. Variant cDNA sequences were identified in three of five individuals with known FCGR3 variants. We conclude that FCGR3 gene variants are differentially transcribed between cell types and tissues, increasing the likelihood of the presence of variant FcgammaRIII receptors on the cell surface. The significance of the high number of variant clones in buccal cells, however, is unclear.

[FCGR3B gene frequencies and FCGR3 gene variants in Chinese: a study in 487 Chinese individuals from Zhejiang Province].

OBJECTIVE: To investigate the FCGR3B gene frequencies and FCGR3 variants in a Chinese population from Zhejiang Province. METHODS: DNA was extracted from the blood specimens of 487 healthy blood donors from Zhejiang Province. The FCGR3B gene frequencies were determined by polymerase chain reaction with sequence-specific primers (PCR-SSP). The 19 specimens with 3 different FCGR3B genotypes underwent FCGR3 gene cloning and sequencing. RESULTS: The gene frequencies of FCGR3B(*1), FCGR3B(*2), and FCGR3B(*3) in these 487 individuals were 0.564, 0.429, and 0.000 respectively. The genotype frequency of FCGR3B(null) was 0.62% (3/487). Sequencing of FCGR3 revealed that in 7 out of the 19 Chinese individuals variants caused by single nucleotide exchanges at one or more of the polymorphic positions 141, 147, 227, 266 and 277 in exon 3 also existed in this Chinese population. CONCLUSION: FCGR3B(*1) gene is more frequent in a Chinese population from Zhejiang Province than the FCGR3B(*2) gene, and the FCGR3B(*3) gene seems to be absent. Gene variants caused by single nucleotide exchanges are found in addition to the well known forms, but the reason for this remains unclear.

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 FCGR3B*1 (NA1), FCGR3B*2 (NA2), and FCGR3B*3 (SH) by allele-specific PCR. In a subset of FCGR3B*3-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, FCGR3B*3 was found exclusively in individuals carrying FCGR3B*1 independent of the existence of FCGR3B*2 at a frequency of 5 percent. In the individuals from Uganda, each possible combination of FCGR3B*1, FCGR3B*2, and FCGR3B*3 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.