Investigators:
Andrea
J. Apter, MD, MSc (PI), Timothy Rebbeck, PhD, Athanasios I. Zavras, DMD, MS, DrMS, Richard
Aplenc, MD, MSCE, Richard Spielman, PhD, Alexander Steven Whitehead,
PhD,
Angela Haczku, MD, PhD
Do Genetic Susceptibilities
Play a Role
in Penicillin Allergy?
The goal of this HPE research is to
use penicillin allergy as a model for studying
genetic factors influencing medication responses with properties that
are
difficult to study, e.g. when the response is intermittent,
unanticipated,
potentially life-threatening, has no gold standard phenotypic
definition, or
for which no generally accepted animal model exists. As penicillin
allergy has
all of these properties, it is a fitting model for exploring design and
methodologies to address one or more of these problems.
Our
Specific Aims are to:
- Develop
methods for studying medication responses that
are intermittent, unanticipated, potentially life-threatening, or have
no
phenotypic gold standard, using penicillin allergy as a model.
- Design
and test methods of identifying and obtaining
genetic material from patients with these medication responses, from
large
clinical databases in collaboration with investigators from Ingenix,
using the
claims database of United Health Care.
- Establish
a
transdisciplinary collaboration and apprenticeship of
allergy-immunology, drug
allergy, epidemiology, genetics, pharmacology, and the health care
industry for
addressing Aims 1 and 2.
Our two hypotheses related
to penicillin allergy are
that: 1) polymorphisms of genes whose
products participate in the immediate hypersensitivity response, e.g., genes from Chromosome 5q23-35 whose products
include IL-4, IL-13, IL-9, IL –5, and IL-3, are associated with
increased risk of hypersensitivity and 2) products of polymorphisms of
drug
metabolism genes, e.g. CYP3A4,
metabolize penicillin differently, enhancing
its immunogenicity.
Through our interdisciplinary collaboration and with
Dr. Apter’s apprenticeship we will obtain appropriate pilot data for a
successful application for external funding.