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.