Neutrophil-specific antigens HNA-1a(NA1) and HNA-1b(NA2) are located on Fc-gamma-receptor IIIb(FcRIIIb). NA1 and NA2 forms of FcgRIIIb differ by four amino acids and the corresponding genes by five nucleotides. Variations in NA gene frequencies are encountered among ethnic groups. Altered forms of the genes are expected among individuals. We used restriction fragment length polymorphisms (RFLPs) associated with four recognition sites to determine NA genotypes of 232 individuals. When atypical NA genotypes were identified, FcgRIIIB and FcgRIIIA regions were sequenced. NA1-FcgRIIIB frequency in 100 Japanese (0.66) was greater than in 53 African-Americans (0.40; p< 0.01) and 79 Caucasians (0.32; p< 0.001). Sequencing atypical FcgRIIIB in 16 people confirmed four African Americans had GA substitutions at 227; seven African Americans had AG substitutions at 277; one Japanese had CG at 141 and GT at 227. A at 227 and G at 277 represent expected nucleotides of NA1- FcgRIIIB. One African-American had an NA1-FcgRIIIB with a GA substitution at 349; A is normally found in NA2-FcgRIIIB at 349. Sequencing atypical FcgRIIIA in three people revealed two African Americans had GA sub-stitutions at 277 plus CA substitutions at 266 and one Caucasian had previously described TG at 230. Two African-Americans with atypical NA2-FcgRIIIB had TG FcgRIIIA at 230. One African-American was NA-null. NA2-FcgRIIIB is more polymorphic in African Americans than in Caucasians or Japanese. Chimeric FcgRIIIB alleles are most similar to NA2-FcgRIIIB. One alternate allele of NA1 (NA1*02) and four alternate alleles of NA2 (NA2*02, NA2*03, NA2*04, and NA2*05) are described. The expression of NA1-FcgRIIIB and NA2-FcgRIIIB on granulocytes from these donors is being studied.
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