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Pharmacogenetics of inhaled long‐acting beta2‐agonists in asthma: A systematic review
Author(s) -
Slob Elise M. A.,
Vijverberg Susanne J. H.,
Palmer Colin N. A.,
Zazuli Zulfan,
Farzan Niloufar,
Oliveri Nadia M. B.,
Pijnenburg Mariëlle W.,
Koppelman Gerard H.,
Maitlandvan der Zee Anke H.
Publication year - 2018
Publication title -
pediatric allergy and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.269
H-Index - 89
eISSN - 1399-3038
pISSN - 0905-6157
DOI - 10.1111/pai.12956
Subject(s) - medicine , asthma , pharmacogenetics , observational study , meta analysis , clinical trial , systematic review , medline , pediatrics , genotype , gene , biochemistry , chemistry , political science , law
Background Long‐acting beta2‐agonists ( LABA ) are recommended in asthma therapy; however, not all asthma patients respond well to LABA . We performed a systematic review on genetic variants associated with LABA response in patients with asthma. Methods Articles published until April 2017 were searched by two authors using PubMed and EMBASE . Pharmacogenetic studies in patients with asthma and LABA response as an outcome were included. Results In total, 33 studies were included in this systematic review; eight focused on children (n = 6051). Nineteen studies were clinical trials, while 14 were observational studies. Studies used different outcomes to define LABA response, for example, lung function measurements ( FEV 1 , PEF , MMEF , FVC ), exacerbations, quality of life, and asthma symptoms. Most studies (n = 30) focused on the ADRB 2 gene, encoding the beta2‐adrenergic receptor. Thirty studies (n = 14 874) addressed ADRB 2 rs1042713, 7 ADRB 2 rs1042714 (n = 1629), and 3 ADRB 2 rs1800888 (n = 1892). The association of ADRB 2 rs1042713 and rs1800888 with LABA response heterogeneity was successfully replicated. Other variants were only studied in three studies but not replicated. One study focused on the ADCY 9 gene. Five studies and a meta‐analysis found an increased risk of exacerbations in pediatrics using LABA carrying one or two A alleles ( OR 1.52 [1.17; 1.99]). These results were not confirmed in adults. Conclusions ADRB 2 rs1042713 variant is most consistently associated with response to LABA in children but not adults. To assess the clinical value of ADRB 2 rs1042713 in children with asthma using LABA , a randomized clinical trial with well‐defined outcomes is needed.