β₂-adrenergic receptor polymorphisms, asthma and COPD: two large population-based studies

Abstract

The b 2 -adrenergic receptor (ADRB2) is an important regulator of airway smooth muscle tone. We tested the hypothesis that three functional polymorphisms in the ADRB2 gene (Thr164Ile, Gly16Arg and Gln27Glu) are associated with reduced lung function, asthma or chronic obstructive pulmonary disease (COPD).We first genotyped 8,971 individuals from the Copenhagen City Heart Study for all three polymorphisms. To validate our findings, we genotyped an additional 53,777 individuals from the Copenhagen General Population Study for the Thr164Ile polymorphism.We identified 60,910 Thr164Ile noncarriers, 1,822 heterozygotes and 16 homozygotes. In the Copenhagen City Heart Study, the Thr164Ile genotype was associated with reduced forced expiratory volume in 1 s (FEV1) % predicted (trend p50.01) and FEV1/forced vital capacity (FVC) (p50.001): Thr164Ile heterozygotes had 3% and 2% reduced FEV1 % pred and FEV1/FVC, respectively, compared with noncarriers. The odds ratio for COPD in Thr164Ile heterozygotes was 1.46 (95% CI 1.05-2.02). In the Copenhagen General Population Study, the Thr164 genotype associated with reduced FEV1 % pred (p50.04) and FEV1/FVC (p,0.001): Thr164Ile homozygotes and heterozygotes had 7% and 1% reduced FEV1 % pred and 6% and 1% reduced FEV1/FVC, respectively, compared with noncarriers. The odds ratios for COPD in Thr164Ile homozygotes and heterozygotes were 4.53 (95% CI 1.54-13.3) and 1.07 (95% CI 0.92-1.25), respectively.Our results suggest that ADRB2 Thr164Ile is associated with reduced lung function and increased risk of COPD in the general population.

Polymorphic Variants of Adrenoceptors: Pharmacology, Physiology, and Role in Disease

“…The largest of these studies (.60,000 individuals) was recently published and yielded a (relatively weak) association of the Ile variant at position 164 with reduced lung function and increased risk of COPD in the general population, albeit no association of the variants at positions 16 and 27 with reduced lung function, asthma, or COPD was reported (Thomsen et al, 2012b). In contrast with the latter large candidate gene study, none of the 18 large (n .…”

Chronic Obstructive Pulmonary Disease: Official diagnosis and treatment guidelines of the Czech Pneumological and Phthisiological Society; a novel phenotypic approach to COPD with patient-oriented care

“…A combination of ICS + LABA + LAMA represents another recommended therapy of this phenotype. Subsequently, the therapy can be complemented with antileukotrienes 3,[80][81][82] .…”

ADRB2 gene polymorphism: a role for predisposition, course and therapeutic response in chronic obstructive pulmonary disease

“…Таким образом, по результатам исследования было предположено, что генотип Thr164/Ile164 ассоци ирован со сниженной легочной функцией и повы шенным риском развития ХОБЛ в общей популя ции [25].…”

“…Таким образом, ал лельные варианты ADRB2 гена в положении 16 и 27 не влияют на предрасположенность к ХОБЛ и легоч ную функцию, тяжесть заболевания. Кроме того, было выявлено различие между европейской и ази атской популяциями в распределении генотипов в положениях 16 и 27 (p < 0,05, кроме генотипа Arg16/Gly16) [24].В ноябре 2011 г. были опубликованы результаты 2 больших популяционных исследований, целью ко торых стала оценка роли полиморфизмов гена β2 ад ренергического рецептора в развитии БА и ХОБЛ [25]. Первоначально был генотипирован 8 971 пациент, участвовавший в исследовании Copenhagen City Heart Study, на все 3 полиморфизма.…”