# Pharmacogenomic and Metabolic Optimization of Glucocorticoid Therapy for Asthma

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $655,506

## Abstract

Abstract:
Personalized glucocorticoid (GC) therapy for asthma and other diseases could become a reality if specific
genetic markers were strongly associated with an individual patient's response to therapy. Our studies have
identified 2 inactivating single nucleotide polymorphisms (SNPs) in Cytochrome P450 3A4 and CYP3A5
enzymes that show improved responses to inhaled GCs among children with asthma. We propose these SNPs
slow airway and systemic clearance of inhaled GCs, prolonging their anti-inflammatory effects, thereby providing
superior asthma control. These clinical observations are further supported by in vitro studies of GC metabolism
by the CYP3A enzymes. Building upon these exciting findings, we hypothesize that asthma control with GCs
can be improved by using a patient's genetic profile for CYP3A and related genes to guide both the selection of
an appropriate GC, its dose, and perhaps other adjuvant therapies. We propose to test this hypothesis through
the following tasks: 1) Identify additional genotype:inhaled GC efficacy:asthma control correlations in children
with asthma; 2) conduct a pharmacokinetic study with patients to measure systemic clearance of fluticasone
propionate (FP) and beclomethasone dipropionate (BDP), relative to CYP3A4 and CYP3A5 genotype -
specifically the effects of CYP3A4*22 and CYP3A5*3 versus wild-type genotypes, respectively; and 3)
demonstrate longitudinal associations between asthma symptom control for medication:genotype combinations
using a novel patient monitoring system, the electronic Asthma Tracker (e-AT), to measure medication
compliance, combined with physiologic assessments of pulmonary function, which are essential when monitoring
sustained responses to drug therapy. The overall objective of this study is to further understand the biochemical
relationship and clinical significance of the CYP3A4*22:FP and CYP3A5*3:BDP genotype:asthma control
associations and expand these observations to account for other associated genetic variations that impact GC
metabolism, efficacy, and asthma care. Inhaled glucocorticoids (GCs) are the primary medications prescribed to
control asthma. However, GCs fail to control asthma symptoms in up to 50% of people. Thus, it is critical to
understand factors that limit efficacy in order to guide the selection of the best treatment to maximize benefit and
reduce healthcare costs. We expect these studies to explain our findings on CYP3A4 and 3A5 and to reveal new
relationships between asthma control, GCs and SNPs in various components of the “CYP3A enzyme system”
which can be used as a framework to improve asthma care using GCs.

## Key facts

- **NIH application ID:** 9829106
- **Project number:** 5R01GM121648-04
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Christopher A Reilly
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $655,506
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9829106

## Citation

> US National Institutes of Health, RePORTER application 9829106, Pharmacogenomic and Metabolic Optimization of Glucocorticoid Therapy for Asthma (5R01GM121648-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9829106. Licensed CC0.

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