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

BACKGROUND: 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. STUDY DESIGN AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.