LTA4H rs2660845 association with montelukast response in early and late-onset asthma
| العنوان: | LTA4H rs2660845 association with montelukast response in early and late-onset asthma |
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| المؤلفون: | Glenda Lassi, Maria Pino-Yanes, Somnath Mukhopadhyay, Roger Tavendale, Antonio Espuela-Ortiz, Karen Wilson, Natalia Hernandez-Pacheco, Colin N. A. Palmer, Simon Young, Steve Turner, Adam Platt, Cyrielle Maroteau, Fiona Carr, Esteban G. Burchard, Anke-Hilse Maitland-van der Zee, Esther Herrera-Luis, James D. Chalmers, Sundararajan Srinivasan |
| المساهمون: | Pulmonology, Paediatric Pulmonology, AII - Inflammatory diseases, APH - Personalized Medicine |
| المصدر: | PLoS ONE, 16(9 September):e0257396. Public Library of Science PLoS ONE PLoS ONE, Vol 16, Iss 9, p e0257396 (2021) |
| بيانات النشر: | Public Library of Science, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e583b11172691656d2a829454145a0c7 http://sro.sussex.ac.uk/id/eprint/101847/5/journal.pone.0257396.pdf |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e583b11172691656d2a829454145a0c7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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