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

Jianming Wu, Yunfang Li, Randy M. Schuller, Ling Li, Anne Sophie Litmeyer, Gregor Bein, Ulrich J. Sachs, Behnaz Bayat

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1836-1842
Number of pages7
JournalTransfusion
Volume59
Issue number5
DOIs
StatePublished - May 1 2019

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Medical Genetics
Single Nucleotide Polymorphism
Neutrophils
Antigens
Genotype
Tissue Donors
Blood Donors
Phenotype
Isoantibodies
DNA Sequence Analysis
Healthy Volunteers
Flow Cytometry
Complementary DNA

PubMed: MeSH publication types

  • Journal Article

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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. / Wu, Jianming; Li, Yunfang; Schuller, Randy M.; Li, Ling; Litmeyer, Anne Sophie; Bein, Gregor; Sachs, Ulrich J.; Bayat, Behnaz.

In: Transfusion, Vol. 59, No. 5, 01.05.2019, p. 1836-1842.

Research output: Contribution to journalArticle

Wu, Jianming ; Li, Yunfang ; Schuller, Randy M. ; Li, Ling ; Litmeyer, Anne Sophie ; Bein, Gregor ; Sachs, Ulrich J. ; Bayat, Behnaz. / The nonconservative CD177 single-nucleotide polymorphism c.1291G>A is a genetic determinant for human neutrophil antigen-2 atypical/low expression and deficiency. In: Transfusion. 2019 ; Vol. 59, No. 5. pp. 1836-1842.
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title = "The nonconservative CD177 single-nucleotide polymorphism c.1291G>A is a genetic determinant for human neutrophil antigen-2 atypical/low expression and deficiency",
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.",
author = "Jianming Wu and Yunfang Li and Schuller, {Randy M.} and Ling Li and Litmeyer, {Anne Sophie} and Gregor Bein and Sachs, {Ulrich J.} and Behnaz Bayat",
year = "2019",
month = "5",
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doi = "10.1111/trf.15222",
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TY - JOUR

T1 - The nonconservative CD177 single-nucleotide polymorphism c.1291G>A is a genetic determinant for human neutrophil antigen-2 atypical/low expression and deficiency

AU - Wu, Jianming

AU - Li, Yunfang

AU - Schuller, Randy M.

AU - Li, Ling

AU - Litmeyer, Anne Sophie

AU - Bein, Gregor

AU - Sachs, Ulrich J.

AU - Bayat, Behnaz

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

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