Variants of the ADRB2 Gene in COPD: Systematic Review and Meta-Analyses of Disease Risk and Treatment Response

Abstract

The β-adrenergic receptor (ADRB) is an important regulator of airway smooth muscle tone in chronic obstructive pulmonary disease (COPD). Variants that impair ADRB function could increase disease risk or reduce the response to endogenous and inhaled adrenergic agonists in COPD. We performed a systematic review and three meta-analyses to assess whether three functional variants (Thr164Ile, Arg16Gly, and Gln27Glu) in the ADRB gene are associated with elevated risk of disease or reduced therapeutic response to inhaled β-agonists in COPD. We searched the medical literature from 1966 to 2017 and found 16 relevant studies comprising 85381 study subjects. The meta-analyses found no significant association between ADRB genotype and COPD risk. The summary odds ratios (ORs) for COPD in Thr164Ile homozygotes and heterozygotes were 2.57 (95% confidence interval (CI): 0.54-12.4) and 1.17 (95% CI: 0.96-1.44), respectively. Corresponding summary ORs for COPD in Arg16Gly homozygotes and heterozygotes were 0.97 (95% CI: 0.76-1.22) and 1.01 (95% CI: 0.81-1.26), while summary ORs for COPD in Gln27Glu homozygotes and heterozygotes were 1.00 (95% CI: 0.80-1.25) and 0.94 (95% CI: 0.69-1.24), respectively. When stratified by ethnicity, the summary ORs for COPD did not differ from 1.0 for any of the ADRB variants among Asian, Caucasian, or African populations. We found no consistent associations between ADRB genotype and treatment response to inhaled β-agonists in COPD. This systematic review and meta-analyses found that COPD risk and response to inhaled β-agonists were not associated with Thr164Ile, Arg16Gly, and Gln27Glu genotypes. However, identified cases of Thr164Ile were few, and additional studies of rare ADRB genotypes are required.

HSP90AA1, ADRB2, TBL1XR1 and HSPB1 are chronic obstructive pulmonary disease‑related genes that facilitate squamous cell lung cancer progression

“…The microarray analysis employed in the current study revealed that ADRB2 and HSP90AA1 are downregulated in SCC tissues compared with healthy adjacent non-cancerous tissue, suggesting that they may serve important roles in the progression of SCC. Previous studies reported that ADRB2 is an important regulator of airway smooth muscle tone (14)(15)(16). High levels of ADRB2 are associated with reduced lung function, asthma and COPD (14).…”

“…Previous studies reported that ADRB2 is an important regulator of airway smooth muscle tone (14)(15)(16). High levels of ADRB2 are associated with reduced lung function, asthma and COPD (14). Additionally, ADRB2 is an anti-inflammatory gene and was previously reported to be involved in hyperinflammation (17) and autoimmune disorders such as rheumatoid arthritis (18).…”

Epidemiology of Chronic Obstructive Pulmonary Disease in Brazil: a systematic review and meta-analysis

“…Systematic reviews of COPD prevalence have been limited to risk factors [6][7][8][9][10][11][12] , clinical complications [13][14][15] , comorbidities 16 , economic impact [17][18][19] , and treatment of the disease [20][21][22] . However, the scientific evidence about the occurrence of COPD in populations in developing countries, like Brazil, is limited.…”

An investigation of the association between ADRB2 gene polymorphisms and asthma in Kazakh population

“…Previous studies do not allow drawing an unequivocal conclusion about the involvement of ADRB2 polymorphisms in predisposition of COPD and response of COPD patients to treatment with beta‐2‐agonists. Meta‐analyses included 85 381 studies’ participants and did not find a significant association of Arg16Gly and Gln27Glu polymorphisms with the risk of disease and therapeutic effects of inhaled beta‐2‐agonists. Hussein et al revealed an association of the Arg16 genotypes with highly pronounced respiratory symptoms and frequent exacerbations in Egyptian patients with COPD, and these findings were consistent with our data.…”