TY - JOUR
T1 - Variants of the ADRB2 Gene in COPD
T2 - Systematic Review and Meta-Analyses of Disease Risk and Treatment Response
AU - Nielsen, Anne Orholm
AU - Jensen, Camilla Steen
AU - Arredouani, Mohamed Simo
AU - Dahl, Ronald
AU - Dahl, Morten
PY - 2017/7/4
Y1 - 2017/7/4
N2 - The β2-adrenergic receptor (ADRB2) is an important regulator of airway smooth muscle tone in chronic obstructive pulmonary disease (COPD). Variants that impair ADRB2 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 ADRB2 gene are associated with elevated risk of disease or reduced therapeutic response to inhaled β2-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 ADRB2 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 ADRB2 variants among Asian, Caucasian, or African populations. We found no consistent associations between ADRB2 genotype and treatment response to inhaled β2-agonists in COPD. This systematic review and meta-analyses found that COPD risk and response to inhaled β2-agonists were not associated with Thr164Ile, Arg16Gly, and Gln27Glu genotypes. However, identified cases of Thr164Ile were few, and additional studies of rare ADRB2 genotypes are required.
AB - The β2-adrenergic receptor (ADRB2) is an important regulator of airway smooth muscle tone in chronic obstructive pulmonary disease (COPD). Variants that impair ADRB2 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 ADRB2 gene are associated with elevated risk of disease or reduced therapeutic response to inhaled β2-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 ADRB2 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 ADRB2 variants among Asian, Caucasian, or African populations. We found no consistent associations between ADRB2 genotype and treatment response to inhaled β2-agonists in COPD. This systematic review and meta-analyses found that COPD risk and response to inhaled β2-agonists were not associated with Thr164Ile, Arg16Gly, and Gln27Glu genotypes. However, identified cases of Thr164Ile were few, and additional studies of rare ADRB2 genotypes are required.
KW - Administration, Inhalation
KW - Adrenergic beta-2 Receptor Agonists/administration & dosage
KW - African Continental Ancestry Group/genetics
KW - Asian Continental Ancestry Group/genetics
KW - Bronchodilator Agents/administration & dosage
KW - European Continental Ancestry Group/genetics
KW - Genetic Predisposition to Disease
KW - Genotype
KW - Humans
KW - Pulmonary Disease, Chronic Obstructive/drug therapy
KW - Receptors, Adrenergic, beta-2/genetics
KW - Risk Factors
KW - Treatment Outcome
U2 - 10.1080/15412555.2017.1320370
DO - 10.1080/15412555.2017.1320370
M3 - Review
C2 - 28506092
SN - 1541-2555
VL - 14
SP - 451
EP - 460
JO - COPD: Journal of Chronic Obstructive Pulmonary Disease
JF - COPD: Journal of Chronic Obstructive Pulmonary Disease
IS - 4
ER -