LTA4H rs2660845 association with montelukast response in early and late-onset asthma.
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 the LTA4H regulatory variant rs2660845 and age of asthma onset in response to montelukast in ethnic...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/336ae4e495164e158dd79d9dc9b0ed2d |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:336ae4e495164e158dd79d9dc9b0ed2d |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:336ae4e495164e158dd79d9dc9b0ed2d2021-12-02T20:06:11ZLTA4H rs2660845 association with montelukast response in early and late-onset asthma.1932-620310.1371/journal.pone.0257396https://doaj.org/article/336ae4e495164e158dd79d9dc9b0ed2d2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0257396https://doaj.org/toc/1932-6203Leukotrienes 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 the LTA4H regulatory 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 in LTA4H, 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 of LTA4H activity. These findings support a precision medicine approach for the treatment of asthma with montelukast.Cyrielle MaroteauAntonio Espuela-OrtizEsther Herrera-LuisSundararajan SrinivasanFiona CarrRoger TavendaleKaren WilsonNatalia Hernandez-PachecoJames D ChalmersSteve TurnerSomnath MukhopadhyayAnke-Hilse Maitland-van der ZeeEsteban G BurchardMaria Pino-YanesSimon YoungGlenda LassiAdam PlattColin N A PalmerPiCA ConsortiumPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0257396 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Cyrielle Maroteau Antonio Espuela-Ortiz Esther Herrera-Luis Sundararajan Srinivasan Fiona Carr Roger Tavendale Karen Wilson Natalia Hernandez-Pacheco James D Chalmers Steve Turner Somnath Mukhopadhyay Anke-Hilse Maitland-van der Zee Esteban G Burchard Maria Pino-Yanes Simon Young Glenda Lassi Adam Platt Colin N A Palmer PiCA Consortium LTA4H rs2660845 association with montelukast response in early and late-onset asthma. |
| description |
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 the LTA4H regulatory 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 in LTA4H, 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 of LTA4H activity. These findings support a precision medicine approach for the treatment of asthma with montelukast. |
| format |
article |
| author |
Cyrielle Maroteau Antonio Espuela-Ortiz Esther Herrera-Luis Sundararajan Srinivasan Fiona Carr Roger Tavendale Karen Wilson Natalia Hernandez-Pacheco James D Chalmers Steve Turner Somnath Mukhopadhyay Anke-Hilse Maitland-van der Zee Esteban G Burchard Maria Pino-Yanes Simon Young Glenda Lassi Adam Platt Colin N A Palmer PiCA Consortium |
| author_facet |
Cyrielle Maroteau Antonio Espuela-Ortiz Esther Herrera-Luis Sundararajan Srinivasan Fiona Carr Roger Tavendale Karen Wilson Natalia Hernandez-Pacheco James D Chalmers Steve Turner Somnath Mukhopadhyay Anke-Hilse Maitland-van der Zee Esteban G Burchard Maria Pino-Yanes Simon Young Glenda Lassi Adam Platt Colin N A Palmer PiCA Consortium |
| author_sort |
Cyrielle Maroteau |
| title |
LTA4H rs2660845 association with montelukast response in early and late-onset asthma. |
| title_short |
LTA4H rs2660845 association with montelukast response in early and late-onset asthma. |
| title_full |
LTA4H rs2660845 association with montelukast response in early and late-onset asthma. |
| title_fullStr |
LTA4H rs2660845 association with montelukast response in early and late-onset asthma. |
| title_full_unstemmed |
LTA4H rs2660845 association with montelukast response in early and late-onset asthma. |
| title_sort |
lta4h rs2660845 association with montelukast response in early and late-onset asthma. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/336ae4e495164e158dd79d9dc9b0ed2d |
| work_keys_str_mv |
AT cyriellemaroteau lta4hrs2660845associationwithmontelukastresponseinearlyandlateonsetasthma AT antonioespuelaortiz lta4hrs2660845associationwithmontelukastresponseinearlyandlateonsetasthma AT estherherreraluis lta4hrs2660845associationwithmontelukastresponseinearlyandlateonsetasthma AT sundararajansrinivasan lta4hrs2660845associationwithmontelukastresponseinearlyandlateonsetasthma AT fionacarr lta4hrs2660845associationwithmontelukastresponseinearlyandlateonsetasthma AT rogertavendale lta4hrs2660845associationwithmontelukastresponseinearlyandlateonsetasthma AT karenwilson lta4hrs2660845associationwithmontelukastresponseinearlyandlateonsetasthma AT nataliahernandezpacheco lta4hrs2660845associationwithmontelukastresponseinearlyandlateonsetasthma AT jamesdchalmers lta4hrs2660845associationwithmontelukastresponseinearlyandlateonsetasthma AT steveturner lta4hrs2660845associationwithmontelukastresponseinearlyandlateonsetasthma AT somnathmukhopadhyay lta4hrs2660845associationwithmontelukastresponseinearlyandlateonsetasthma AT ankehilsemaitlandvanderzee lta4hrs2660845associationwithmontelukastresponseinearlyandlateonsetasthma AT estebangburchard lta4hrs2660845associationwithmontelukastresponseinearlyandlateonsetasthma AT mariapinoyanes lta4hrs2660845associationwithmontelukastresponseinearlyandlateonsetasthma AT simonyoung lta4hrs2660845associationwithmontelukastresponseinearlyandlateonsetasthma AT glendalassi lta4hrs2660845associationwithmontelukastresponseinearlyandlateonsetasthma AT adamplatt lta4hrs2660845associationwithmontelukastresponseinearlyandlateonsetasthma AT colinnapalmer lta4hrs2660845associationwithmontelukastresponseinearlyandlateonsetasthma AT picaconsortium lta4hrs2660845associationwithmontelukastresponseinearlyandlateonsetasthma |
| _version_ |
1718375415722016768 |