The Influence of Beta-2 Adrenergic Receptor Gene Polymorphisms on Albuterol Therapy for Patients With Asthma: Protocol for a Systematic Review and Meta-Analysis

BACKGROUND: Albuterol is one of the most frequently used medications in clinical practice and seeing varying responses to albuterol between individuals is not uncommon. Multiple studies have been conducted to investigate the associations of differing responses due to albuterol, particularly with regards to the two nonsynonymous single nucleotide polymorphisms (SNPs) at positions 16 (Arg16Gly: substitution of arginine to glycine at position 16; rs1042713) and 27 (Glu27Gln: substitution of glutamic acid to glutamine at position 27; rs1042714) on the β-2 adrenergic receptor (ADRB2) gene. However, the directions of the correlations are conflicting. OBJECTIVE: The objective of this systematic review and meta-analysis is to assess the effect of the two SNPs on the ADRB2 gene, in terms of the responses that present in asthmatic patients shortly after albuterol inhalation. METHODS: The primary outcome of this work is a detailed study of the associations of the two SNPs in the ADRB2 gene with treatment response and lung function testing shortly after administration of albuterol to asthmatic patients. A comprehensive literature search, using the OVID platform, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, will be conducted by a specialized librarian without language restrictions. We will include both prospective and retrospective original observational studies, and we will exclude nonhuman or in vitro studies. All abstracts will be reviewed by two authors who will also individually perform data extraction from each eligible study. Any arising disagreements will be resolved through discussion with a third party. Risk of bias for all included studies will be independently assessed using the quality of genetic association studies tool. We will report the systematic review and meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A narrative synthesis of study results or meta-analyses will be undertaken when appropriate. RESULTS: At the moment of writing, we have already started the preliminary literature search and piloting of the study selection process. The anticipated completion date is September 30, 2019. CONCLUSIONS: Our systematic review and meta-analysis aims to clarify the current evidence of associations between the two nonsynonymous SNPs in the ADRB2 gene and the responses that present in asthmatic patients shortly after albuterol inhalation. If positive correlations are found, this knowledge may be used to improve personalized pharmacotherapy of albuterol use. TRIAL REGISTRATION: PROSPERO CRD42019074554; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=74554 INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/14759