Frequencies of SLC44A2 alleles encoding human neutrophil antigen-3 variants in the African American population.

The human neutrophil antigen-3 (HNA-3) epitopes reside on the choline transporter-like protein-2 (CTL2). A single-nucleotide substitution (461G>A; Arg154Gln) on the CTL2 gene (SLC44A2) defines the allele SLC44A2*1, which expresses HNA-3a, and SLC44A2*2, which expresses HNA-3b; an additional substitution (457C>T; Leu153Phe) in SLC44A2*1:2 may impact genotyping systems. People who only express HNA-3b may develop anti-HNA-3a. These alloantibodies have been linked to severe transfusion-related acute lung injury, which may be a reason to screen blood donors for SLC44A2*2 homozygosity. For Caucasian and Asian populations, SLC44A2 allele frequencies are known. Our primary objective was to determine the SLC44A2 allele frequencies in the African American population. Purified DNA from 334 individuals (202 male, 132 female; 241 African American, 93 Caucasian) was collected. Two real-time polymerase chain reaction assays were developed to genotype all samples; results were confirmed by nucleotide sequencing. In 241 African American donors, the allele frequency of SLC44A2*1 was 93% (85%-<100%; 95% confidence intervals, Poisson distribution) while SLC44A2*2 was 7% (5%-10%). In 93 Caucasian donors, the allele frequency of SLC44A2*1 was 83% (71%-98%) and SLC44A2*2 was 17% (11%-24%), matching previously reported data for Caucasians but differing from African Americans (p < 0.001, Fisher's exact test). This study describes the allele frequencies of the three known HNA-3 variants in an African American population. We found that African Americans have a significantly lower probability of possessing the SLC44A2*2 allele and may thus be less likely to form the clinically relevant anti-HNA-3a.