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Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Predicting inhaled corticosteroid response in asthma with two associated SNPs.
M J McGeachie1, A C Wu, H-H Chang
1Partners Healthcare Center for Personalized Genetic Medicine, Boston, MA, USA.
The Pharmacogenomics Journal
|May 30, 2012
Summary
Two genetic markers predict inhaled corticosteroid (ICS) response in asthma patients. This combined genetic test identifies individuals with good or poor treatment outcomes, offering improved accuracy over single markers.
Area of Science:
- Pharmacogenomics
- Respiratory Medicine
- Genetics
Background:
- Inhaled corticosteroids (ICS) are primary controller medications for asthma management.
- Previous research identified two single-nucleotide polymorphisms (SNPs), rs1876828 and rs37973, linked to corticosteroid treatment efficacy.
- Asthma patient response to ICS can vary significantly.
Purpose of the Study:
- To develop and validate a predictive genetic test for inhaled corticosteroid (ICS) response in asthma patients.
- To combine two specific SNPs (rs1876828 and rs37973) into a single predictive model.
- To assess the accuracy and replicability of this combined genetic test compared to individual SNP predictors.
Main Methods:
- Utilized data from four existing clinical trials involving asthma patients treated with ICS.
- Measured lung function, specifically forced expiratory volume in 1 second (FEV1), before and after ICS treatment.
- Employed a Bayesian model to combine rs1876828 and rs37973 SNPs for predicting FEV1 change and classifying patients into good or poor steroid responders.
Main Results:
- The combined SNP test achieved a predictive performance of 65.7% area under the receiver-operator characteristic curve in the training population (P=0.039).
- The test demonstrated replicability with 65.9% predictive performance in the test population (P=0.025).
- The combined test identified patients with good or poor steroid response with significant accuracy.
Conclusions:
- A predictive test combining two genetic variants (rs1876828 and rs37973) can accurately predict ICS response in asthma.
- This dual-SNP approach offers comparable accuracy and superior replicability to single SNP predictors.
- This genetic test holds potential for personalizing asthma treatment strategies.
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