Molecular studies reveal that A134T, G156A and G1333A SNPs in the CD177 gene are associated with atypical expression of human neutrophil antigen-2.
OBJECTIVE
The human neutrophil antigen-2 (HNA-2) is expressed on a subpopulation of neutrophils as most subjects present a negative plus a positive HNA-2 population of neutrophils. The number of neutrophils expressing HNA-2 is variable and may increase in pregnancy, infections, myeloproliferative disorders and after G-CSF. This study investigated the presence of polymorphisms in the gene encoding HNA-2 (CD177) in individuals presenting different patterns of antigen expression and determined the association of single nucleotide polymorphisms (SNPs) with the heterogeneous HNA-2 expression.


METHODS
Flow cytometry was employed to analyse the HNA-2 expression on neutrophils from 135 healthy subjects using two monoclonal antibodies (TAG4, 7D8). Sequencing reactions were performed on subjects whose antigen expression was low (< or = 50%), high (> or = 80%) or atypical (a nonreactive population plus two distinct positive cell populations).


RESULTS
Five SNPs were detected, two of them (A793C, G1084A) were related to a low expression of HNA-2 (P = 0.031 and P = 0.004). Atypical antigen expression was observed in 5.9% (8/135) of the individuals, three nonpregnant women and five men. In these cases, the cDNA sequences revealed three SNPs (A134T, G156A and G1333A) strongly related to this atypical HNA-2 expression (P = 0.004, P = 0.006 and P < 0.0001, respectively).


CONCLUSIONS
Our data show that polymorphisms in the CD177 are associated with variations in the HNA-2 expression and may be the cause of atypical expressions.
Moritz
E
E
Discipline of Hematology and Hemotherapy, Federal University of São Paulo, São Paulo, Brazil.
Chiba
A K
AK
Kimura
E Y
EY
Albuquerque
D
D
Guirão
F P
FP
Yamamoto
M
M
Costa
F F
FF
Bordin
J O
JO
D000328:Adult; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D006801:Humans; D007519:Isoantigens / Q000096:biosynthesis / Q000097:blood / Q000235:genetics* / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000097:blood / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
C407242:CD177 protein, human; D058851:GPI-Linked Proteins; D007519:Isoantigens; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface