The development of a novel molecular assay examining the role of aminopeptidase P
polymorphisms in acute hypotensive transfusion reactions.
CONTEXT: Acute hypotensive transfusion reactions are potentially harmful adverse
effects of transfusion attributable to bradykinin generation. They are most often
seen in patients taking angiotensin-converting enzyme (ACE) inhibitors (ACE-Is)
because of the role ACE plays in metabolizing bradykinin. However, a number of
acute hypotensive transfusion reactions occur in patients not taking ACE-Is.
Aminopeptidase P (APP), another important enzyme responsible for bradykinin
degradation, is encoded by the polymorphic XPNPEP2 gene. Some polymorphisms in
XPNPEP2 have been associated with decreased APP activity. However, the role that
APP polymorphisms play in acute hypotensive transfusion reactions has never been
investigated.
OBJECTIVE: To develop a molecular assay to examine for the C-2399A
single-nucleotide polymorphism (SNP) in the APP gene, XPNPEP2, in patients
experiencing acute hypotensive transfusion reactions unassociated with ACE-Is.
DESIGN: We developed an assay using polymerase chain reaction and DNA sequencing
with primers targeted at XPNPEP2 (5'-GAGTATTATGTGGGGACCATCC-3' and
5'-ATGCCTCGCAGAGACAAGAG-3'). Polymorphism zygosity was determined by comparing
the sense/antisense sequencing results. This assay was then applied to patients
with acute hypotensive transfusion reactions not taking ACE-Is (n = 4).
RESULTS: A C-2399A SNP assay was successfully developed and applied to patients
with acute hypotensive transfusion reactions. In a pilot study, 2 patients (50%)
were found to possess C-2399A polymorphisms. One was found to be homozygous, and
the other was heterozygous.
CONCLUSIONS: Our C-2399A SNP assay can be used to study acute hypotensive
transfusion reactions in patients not taking ACE-Is. Initial data indicate that
the C-2399A polymorphism may be a contributing factor in such reactions. However,
further studies are necessary to better define the role of APP polymorphisms in
relation to acute hypotensive transfusion reactions unassociated with ACE-Is.
Hui Y(1), Wu Y, Tormey CA. Arch Pathol Lab Med. 2013 Jan;137(1):96-9.