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LTA4H rs2660845 association with montelukast response in early and late-onset asthma
- Source :
- PLoS ONE, 16(9 September):e0257396. Public Library of Science, PLoS ONE, PLoS ONE, Vol 16, Iss 9, p e0257396 (2021)
- Publication Year :
- 2021
- Publisher :
- Public Library of Science, 2021.
-
Abstract
- Leukotrienes play a central pathophysiological role in both paediatric and adult asthma. However, 35% to 78% of asthmatics do not respond to leukotriene inhibitors. In this study we tested the role of theLTA4Hregulatory variant rs2660845 and age of asthma onset in response to montelukast in ethnically diverse populations. We identified and genotyped 3,594 asthma patients treated with montelukast (2,514 late-onset and 1,080 early-onset) from seven cohorts (UKBiobank, GoSHARE, BREATHE, Tayside RCT, PAGES, GALA II and SAGE). Individuals under montelukast treatment experiencing at least one exacerbation in a 12-month period were compared against individuals with no exacerbation, using logistic regression for each cohort and meta-analysis. While no significant association was found with European late-onset subjects, a meta-analysis of 523 early-onset individuals from European ancestry demonstrated the odds of experiencing asthma exacerbations by carriers of at least one G allele, despite montelukast treatment, were increased (odds-ratio = 2.92, 95%confidence interval (CI): 1.04–8.18, I2 = 62%, p = 0.0412) compared to those in the AA group. When meta-analysing with other ethnic groups, no significant increased risk of asthma exacerbations was found (OR = 1.60, 95% CI: 0.61–4.19, I2 = 85%, p = 0.342). Our study demonstrates that genetic variation inLTA4H, together with timing of asthma onset, may contribute to variability in montelukast response. European individuals with early-onset (≤18y) carrying at least one copy of rs2660845 have increased odd of exacerbation under montelukast treatment, presumably due to the up-regulation ofLTA4Hactivity. These findings support a precision medicine approach for the treatment of asthma with montelukast.
- Subjects :
- Cyclopropanes
Male
Critical Care and Emergency Medicine
Pulmonology
Exacerbation
Acetates
Logistic regression
law.invention
Geographical Locations
Medical Conditions
Mathematical and Statistical Techniques
0302 clinical medicine
Randomized controlled trial
law
immune system diseases
Odds Ratio
Medicine and Health Sciences
Ethnicities
Anti-Asthmatic Agents
Longitudinal Studies
Age of Onset
Child
African American people
Epoxide Hydrolases
0303 health sciences
Leukotriene
Multidisciplinary
Pharmaceutics
Statistics
Serial Analysis of Gene Expression
Genomics
Middle Aged
Metaanalysis
Population groupings
3. Good health
Hospitalization
Europe
Child, Preschool
Physical Sciences
Cohort
Quinolines
Medicine
Regression Analysis
Female
Transcriptome Analysis
Research Article
medicine.drug
Adult
Risk
medicine.medical_specialty
Adolescent
Genotype
Science
Sulfides
Research and Analysis Methods
Young Adult
Respiratory Disorders
03 medical and health sciences
Drug Therapy
Internal medicine
Gene Expression and Vector Techniques
Genetics
medicine
Humans
Statistical Methods
Allele
Molecular Biology Techniques
Molecular Biology
Alleles
Montelukast
030304 developmental biology
Asthma
Molecular Biology Assays and Analysis Techniques
business.industry
Biology and Life Sciences
Computational Biology
Human Genetics
Genome Analysis
medicine.disease
respiratory tract diseases
Cross-Sectional Studies
030228 respiratory system
Pharmacogenetics
People and Places
Leukotriene Antagonists
business
Receptor Antagonist Therapy
Mathematics
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Database :
- OpenAIRE
- Journal :
- PLoS ONE, 16(9 September):e0257396. Public Library of Science, PLoS ONE, PLoS ONE, Vol 16, Iss 9, p e0257396 (2021)
- Accession number :
- edsair.doi.dedup.....e583b11172691656d2a829454145a0c7