Determination of neutrophil antigen HNA‐3a and HNA‐3b genotype frequencies in six racial groups by high‐throughput 5′ exonuclease assay

Abstract

People with the human neutrophil antigen (HNA)-3b/3b type can make HNA-3a antibodies, which have been reported to cause immune neutropenia disorders and are especially prone to cause severe cases of transfusion-related acute lung injury. However, knowledge of HNA-3 allele frequencies outside Caucasian populations is limited. We developed a high-throughput genotyping assay and determined the HNA-3a/3b genotype frequencies in six different racial and ethnic groups. Genotyping utilized TaqMan 5' exonuclease chemistry and real-time polymerase chain reaction. A total of 742 DNA samples from six different racial and ethnic groups were genotyped for HNA-3a and HNA-3b. The genotyping assay showed 100% sensitivity and specificity compared to sequencing and phenotyping and had high throughput. A significant percentage of Caucasians (6.5%), Han Chinese (16%), and Asian Indians (6%) typed HNA-3b/3b, but only a small percentage of Hispanics (1%) and no African or Native Americans. The HNA-3 genotyping assay had high sensitivity, specificity, and sample throughput. HNA-3b/b genotype results determined for 742 individuals representing six different racial and ethnic groups showed that there could be a significant risk of producing anti-HNA-3a in Chinese, as well as in Caucasian and Asian Indian blood donor populations, but a very low risk in Hispanic, African, or Native American populations.