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The nonconservative CD177 single‐nucleotide polymorphism c.1291G>A is a genetic determinant for human neutrophil antigen‐2 atypical/low expression and deficiency
Author(s) -
Wu Jianming,
Li Yunfang,
Schuller Randy M.,
Li Ling,
Litmeyer AnneSophie,
Bein Gregor,
Sachs Ulrich J,
Bayat Behnaz
Publication year - 2019
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.15222
Subject(s) - genotype , single nucleotide polymorphism , biology , snp , antigen , microbiology and biotechnology , genetics , polymorphism (computer science) , gene
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.