Effect of polymorphisms in the β2-adrenergic receptor on the susceptibility and pulmonary function of patients with chronic obstructive pulmonary disease： a meta analysis

• Published in: Chinese medical journal 2012-06, Vol.125 (12), p.2213-2218
• Main Authors: Niu, Li-Ming, Liang, Ying, Xu, Ming, Zhang, You-Yi, Zhang, Yuan, He, Bei
• Format: Article
• Language: English
• Subjects: Case-Control Studies; Cross-Sectional Studies; Forced Expiratory Volume - physiology; Genetic Predisposition to Disease - genetics; Humans; Polymorphism, Genetic - genetics; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - physiopathology; Receptors, Adrenergic, beta-2 - genetics; Respiratory Function Tests; 基因型频率; 基因多态性; 患者; 慢性阻塞性肺疾病; 慢性阻塞性肺病; 易感性; 肺功能; 肾上腺素受体
• ISSN: 0366-6999; 2542-5641
• DOI: 10.3760/cma.j.issn.0366-6999.2012.12.023

Background Chronic obstructive pulmonary disease （COPD） is a heterogeneous and complex disease of which the pathogenesis remains largely unknown. Many factors could influence COPD development and progression. One of them is the genetic risk factor. A severe hereditary deficiency of alpha-1 antitrypsin is the best genetic proof. Four single nucleotide polymorphisms （SNPs） of beta2-adrenergic receptor （β2AR） result in single amino acid substitution. Two loci had been extensively studied and found that they could change the function of β2AR. Two SNPs consist of substitutions of glycine for arginine at amino acid position 16, glutamic acid for glutamine at position 27. Many studies proved that polymorphisms at position 16 and 27 altered the lung function of COPD patients or the patient＇s susceptibility to the development of COPD. However, there was no exclusive conclusion. Therefore, a meta analysis was done to investigate the effect of polymorphisms in the 62-adrenergic receptor （ADRB2） gene on the risk of COPD and lung function. Methods Comprehensive searches of MEDLINE, Embase, Ovid, HighWire, Cochrane Library, and Chinese databases （CBMdisc, VIP, CNKI, and Wanfang data） from January 1980 to September 2011 were performed, using the keywords： COPD OR chronic obstructive pulmonary disease AND adrenoreceptor OR adrenergic receptor AND polymorphism OR mutation OR variation. Case-control research or cross sectional studies in which diagnosis of COPD met the Global Initiative for Chronic Obstructive Lung Disease （GOLD） guidelines; all the studies reported the ADRB2 genotype at position 16 or 27. Outcomes measured were genotype frequency and forced expiratory volume in the first second （FEV1%） in both the case and control. Results Twelve case-control studies and eight cross-sectional studies were included. Compared to the control （n= 1225）, neither Gly/Gly （n=527） nor Arg/Arg （n=422） homozygotes at position 16 demonstrated increased susceptibility to COPD, with odds ratios （ORs） of 0.95 （95% CI （0.68, 1.31）, z=0.33, P=0.740） and 0.82 （95% CI （0.52, 1.28）, z=0.88, P=0.381）, respectively. Similar results were obtained for position 27, with ORs of 0.97 （95% CI （0.77, 1.23）, z=0.21, P=0.833） for Glu/Glu homozygotes （n=357） and 0.82 （95% CI （0.53, 1.29）, z=0.85, P=0.393） for Gin/Gin homozygotes （n=704） （control=1183）. In patients with COPD, Arg/Arg homozygotes （n=41） had a similar FEV1% compared with Gly/Gly homozygotes （n=102） （standardized mean difference （SMD）=0.88,