Polymorphisms of the beta2 adrenoreceptor gene in chronic obstructive pulmonary disease.
BACKGROUND
The beta2-adrenergic receptors are cell surface receptors playing a central role in the pharmacological targeting asthma and chronic obstructive pulmonary disease [COPD]. Recent studies suggest that patients who are homozygous for one of the two important polymorphisms of the beta2-adrenergic receptor [ADRB2] gene at codon 16 (arginine to glycine) and 27 (glutamine to glutamate) may have a reduced response to ss2-agonists. Since smoking patients who are Gly16 homozygotes have an increased risk of airway obstruction we hypothesized that beta2-adrenoreceptor gene polymorphisms may be also a cofounder for COPD development and disease severity.


METHODS
We investigated 190 COPD patients and 172 healthy volunteers in a case-control study. DNA was isolated from whole blood and beta2-AR gene polymorphisms Arg/Gly16 and Gln/Glu27 were determined using allele-specific polymerase chain reaction [PCR].


RESULTS
In COPD patients with Gly/Gly16 was found more frequently than in healthy smokers [29.47% COPD versus 18.18% controls, p = 0.026]. All other gene polymorphisms of the ADRB2 gene at codon 16 were equally distributed between groups. ss2-adrenoreceptor gene polymorphisms were neither a cofounder for COPD exacerbations [>or= 3 hospitalizations within the last 3 years] nor for disease severity [FEV1 <or= 30% predicted].


CONCLUSIONS
Our study suggests that the Gly16 allele of the beta2-AR gene predisposes to COPD development but not for exacerbation rates and disease severity. In contrast, Gln/Glu27 polymorphism was irrelevant in our COPD cohort.
Vacca
Gabriela
G
St. Georg Medical Center, Robert-Koch-Hospital, Leipzig, Germany.
Schwabe
Kerstin
K
Dück
Ramona
R
Hlawa
Hans-Peter
HP
Westphal
Arite
A
Pabst
Stefan
S
Grohé
Christian
C
Gillissen
Adrian
A
D000368:Aged; D000483:Alleles; D004247:DNA / Q000235:genetics*; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics* / Q000378:metabolism; D012720:Severity of Illness Index
D018343:Receptors, Adrenergic, beta-2; D004247:DNA