Introduction
Asthma is a chronic inflammatory disorder with a multifactorial etiology
characterized by recurrent episodes of coughing, wheezing and dyspnea.
Asthma is a polygenic disease with complex gene-environment interactions[1]. Currently, about 300 million people are
affected by asthma worldwide of which about 250 000 people die per year[2, 3]. The prevalence of asthma varies from 0.2
to 21.0% around the world [3].
Global Initiative for Asthma (GINA) guidelines recommended inhaled
β2-agonists as the first-line rescue treatment for managing acute asthma[4]. Short-acting beta-2 agonists (SABA), the most
effective and widely used bronchodilators presently, are the primary
options for treating acute exacerbations. Salbutamol, one of the
representative drugs of SABA, is an effective medicine to relieve
asthma. However, there are considerable differences in clinical response
to inhaled SABA and 70-80% of the significant heterogeneity can be due
to differences in genetic basis [5]. In addition,
significant variability has been observed in salbutamol response.
Genetic mutations can explain a considerable portion of this variation
and the Beta-2 adrenergic receptor (ADRB2 ) may be a significant
determinant of salbutamol responsiveness [5-7].
ADRB2 gene is an intronless gene located on human chromosome
5q31-32 encoding for the Beta 2 adrenergic receptor (ADRB2)— the
molecular target for beta-2 agonists. Beta-2 agonists selectively bind
to ADRB2 within the cell membrane and relax airway smooth muscle[8]. At least 80 single nucleotide polymorphisms
(SNPs) in the ADRB2 (such as Arg16Gly, Gln27Glu, Val34Met and
Thr164Ile, etc.) have been identified after being resequenced in
multiple populations [9, 10]. Arg16Gly (rs1042713,
A285G) at nucleotide position 46 and Gln27Glu (rs1042714, C318G) at
nucleotide position 79 have been extensively studied among these SNPs
and well described in asthma pharmacogenetics [11,
12]. These ADRB2 mutations change at the ADRB2 amino
acids sequence and alter receptor function, that may lead to the
significant variability in the response to salbutamol[9]. Several previous association studies have
investigated the relationship between ADRB2 polymorphisms
(Arg16Gly, Gln27Glu) and salbutamol responsiveness in asthmatic
patients. However, the results are conflicting among different studies[13-20].
Thus, we conducted this meta-analysis to comprehensively investigate the
effect of the ADRB2 polymorphisms (Arg16Gly, Gln27Glu) on
salbutamol response in asthmatic patients. Then we can identify
individuals who are more likely to respond well to salbutamol and this
will provide evidence for personalized or precision treatment for asthma
improving the effectiveness of the management of asthma.