The nonconservative CD177 single-nucleotide polymorphism c.1291G>A is a genetic determinant for human neutrophil antigen-2 atypical/low expression and deficiency

Transfusion. 2019 May;59(5):1836-1842. doi: 10.1111/trf.15222. Epub 2019 Mar 3.


Background: Human neutrophil antigen-2 (HNA-2) is exclusively expressed on neutrophils. HNA-2-deficient individuals (HNA-2 null) are susceptible to produce isoantibodies. The nonsense CD177 coding single-nucleotide polymorphism (SNP) c.787A>T has been demonstrated as the primary genetic mechanism for HNA-2 deficiency. We hypothesized that the other genetic variants also contribute to HNA-2 expression variation and deficiency.

Study design and methods: The deficiency, density, and percentage of HNA-2 antigen on neutrophils from 292 healthy blood donors were determined in flow cytometry. CD177 genotypes were determined by genomic DNA sequence analyses. The full-length CD177 cDNAs were amplified and sequenced. Additionally, the whole CD177 genomic sequence in eight HNA-2-null immunized women and four HNA-2-positive donors were analyzed with next-generation sequencing. The associations of CD177 SNP genotypes with HNA-2 expression variation were statistically analyzed.

Results: A functional CD177 SNP c.1291G>A was identified in the current study. Atypical (trimodal) HNA-2 expression phenotype was consistently observed in donors carrying the heterozygous c.1291G/A genotype. Phenotype-genotype analyses of SNP c.787A>T and SNP c.1291G>A revealed that all homozygous 787T-1291G (TG/TG) genotype donors were HNA-2 null in healthy blood donors. On the other hand, five of eight HNA-2-immunized females were homozygous for the 787T-1291G (TG/TG) genotype while the other three HNA-2-immunized females had the 787T-1291G/787A-1291A (TG/AA) genotype and the lowest HNA-2 expression was observed in healthy subjects with the 787T-1291G/787A-1291A (TG/AA) and 787A-1291A/787A-1291A (AA/AA) genotype.

Conclusion: The CD177 SNP c.1291G>A is a genetic determinant for the atypical and low HNA-2 expression, which also contributes to HNA-2 deficiency phenotype.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA, Complementary / genetics
  • DNA, Complementary / metabolism
  • Female
  • Flow Cytometry
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Genotype
  • Humans
  • Isoantigens / genetics*
  • Isoantigens / metabolism
  • Neutrophils / metabolism*
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism


  • CD177 protein, human
  • DNA, Complementary
  • GPI-Linked Proteins
  • Isoantigens
  • Receptors, Cell Surface