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

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 β2-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 Gln/Gln 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, 95% CI (–0.85, 2.62), z=1.00, P=0.319). The genotype distribution was different between Caucasian and Asian populations (all P <0.05 except the genotype Arg/Gly) for both position 16 and 27.

Conclusions  Polymorphisms of ADRB2 at positions 16 and 27 did not change the risk of COPD nor affect lung function or disease severity. The genotype distribution for these polymorphisms was different between Caucasian and Asian populations.