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

Abstract

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 (TRALI), 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 PCR 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% to <100%; 95% confidence intervals, Poisson distribution) while SLC44A2*2 was 7% (5% to 10%). In 93 Caucasian donors, the allele frequencies of SLC44A2*1 was 83% (71% to 98%) and SLC44A2*2 was 17% (11% to 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 3 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.

Genotype frequencies of human neutrophil antigen‐3 in the Chinese Zhuang and Dong populations

“…The HNA‐3b/3b genotype frequency among the Zhuang population is 8.6%, which is similar to the frequencies reported in the Dong population of our study and also other Asian populations like Chinese Han, Japanese and Thai shown by previous publications (Changsri et al., ; Matsuhashi et al., ; Xia et al., ) but is significantly higher than that of African American Shown by Huvard et al. (), Brazilian as shown by Lopes et al. () and also English Caucasian populations as revealed by Cardoso et al.…”

“…(), but higher than the African Americans (0.04%) as reported by Huvard et al. (), showing the different potentials of inducing TRALI among different human populations.…”

“…() and the African American blood donors as shown by Huvard et al. (). From the above data, we see that donors in China have a higher propensity of expressing only HNA‐3b which potentially results in production of anti‐HNA‐3a antibodies (Table ).…”

Molecular Genetics of the Human Neutrophil Antigens

“…5). The HNA-3a encoding allele was demonstrated in Caucasians with a frequency of 0.79, in African Americans with 0.93 and in Chinese with 0.74, and the respective HNA-3b-encoding alleles with 0.21, 0.07 and 0.26 [82,83,84]. An additional SLC44A2*451C>T exchange (rs147820753) affecting the amino acid next to Arg152 and inducing a Leu151Phe substitution impairs the HNA-3a epitope in a way that the induction of neutrophil agglutination by some HNA-3a-specific alloantibodies is diminished or even abrogated [85].…”

“…Of note is that this additional mutation can influence HNA-3a typing in HNA-3a/3b heterozygous individuals when the HNA-3a allele-specific sense primer binds with reduced affinity so that the typing result is falsely interpreted as HNA-3b homozygous. This methodical problem can be overcome by applying adequate molecular tests [83,86]. The SLC44A2*451C>T substitution has been demonstrated with a gene frequency of 0.01 and phenotype frequencies of 2.4% in the Caucasian population [80,85] and of 0.4% in African Americans [83].…”