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Pharmacogenetics of inhaled long-acting beta2-agonists in asthma: A systematic review
Slob E.M.A., Vijverberg S.J.H., Palmer C.N.A.b, Zazuli Z.c, Farzan N., Oliveri N.M.B., Pijnenburg M.W.d, Koppelman G.H., Maitland-van der Zee A.H.
a Department of Respiratory Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands
b Population Pharmacogenetics Group, Biomedical Research Centre, University of Dundee, Dundee, United Kingdom
c Department of Pharmacology-Clinical Pharmacy, School of Pharmacy, Bandung Institute of Technology, Bandung, Indonesia
d Department of Paediatrics, Paediatric Pulmonology & Allergology, Erasmus Medical Center-Sophia Children’s Hospital, Rotterdam, Netherlands
e Department of Paediatric, Pulmonology & Paediatric Allergology, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
f Groningen Research Institute for Asthma & COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, Netherlands
[vc_row][vc_column][vc_row_inner][vc_column_inner][vc_separator css=”.vc_custom_1624529070653{padding-top: 30px !important;padding-bottom: 30px !important;}”][/vc_column_inner][/vc_row_inner][vc_row_inner layout=”boxed”][vc_column_inner width=”3/4″ css=”.vc_custom_1624695412187{border-right-width: 1px !important;border-right-color: #dddddd !important;border-right-style: solid !important;border-radius: 1px !important;}”][vc_empty_space][megatron_heading title=”Abstract” size=”size-sm” text_align=”text-left”][vc_column_text]© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.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 (FEV1, PEF, MMEF, FVC), exacerbations, quality of life, and asthma symptoms. Most studies (n = 30) focused on the ADRB2 gene, encoding the beta2-adrenergic receptor. Thirty studies (n = 14 874) addressed ADRB2 rs1042713, 7 ADRB2 rs1042714 (n = 1629), and 3 ADRB2 rs1800888 (n = 1892). The association of ADRB2 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 ADCY9 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: ADRB2 rs1042713 variant is most consistently associated with response to LABA in children but not adults. To assess the clinical value of ADRB2 rs1042713 in children with asthma using LABA, a randomized clinical trial with well-defined outcomes is needed.[/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”Author keywords” size=”size-sm” text_align=”text-left”][vc_column_text]Adenylyl Cyclases,Administration, Inhalation,Adrenergic beta-2 Receptor Agonists,Anti-Asthmatic Agents,Asthma,Humans,Pharmacogenetics,Polymorphism, Genetic,Receptors, Adrenergic, beta-2[/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”Indexed keywords” size=”size-sm” text_align=”text-left”][vc_column_text]asthma,bronchodilator,genetic polymorphism,long-acting beta-agonist,pharmacogenetics[/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”Funding details” size=”size-sm” text_align=”text-left”][vc_column_text][{‘$’: ‘EMAS, SJHV, AHM, GHK, and MWP are conducting the PUFFIN trial that is supported by the Lung Foundation Netherlands, Grant Number 5.1.16.094.’}, {‘$’: ‘trial that is supported by the Lung Foundation Netherlands, Grant’}][/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”DOI” size=”size-sm” text_align=”text-left”][vc_column_text]https://doi.org/10.1111/pai.12956[/vc_column_text][/vc_column_inner][vc_column_inner width=”1/4″][vc_column_text]Widget Plumx[/vc_column_text][/vc_column_inner][/vc_row_inner][/vc_column][/vc_row][vc_row][vc_column][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][/vc_column][/vc_row]