Journalartikel

Jahr der Veröffentlichung: 2019

Seiten: 1836-1842

Zeitschrift: Transfusion

Bandnummer: 59

Heftnummer: 5

ISSN: 0041-1132

eISSN: 1537-2995

Open Access Status: Green

DOI Link: https://doi.org/10.1111/trf.15222

Verlag: Wiley

Abstract: 
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.

Harvard-Zitierstil: Wu, J., Li, Y., Schuller, R., Li, L., Litmeyer, A., Bein, G., et al. (2019) The nonconservative CD177 single-nucleotide polymorphism c.1291G>A is a genetic determinant for human neutrophil antigen-2 atypical/low expression and deficiency, Transfusion, 59(5), pp. 1836-1842. https://doi.org/10.1111/trf.15222

APA-Zitierstil: Wu, J., Li, Y., Schuller, R., Li, L., Litmeyer, A., Bein, G., Sachs, U., & Bayat, B. (2019). The nonconservative CD177 single-nucleotide polymorphism c.1291G>A is a genetic determinant for human neutrophil antigen-2 atypical/low expression and deficiency. Transfusion. 59(5), 1836-1842. https://doi.org/10.1111/trf.15222