Association of beta2-adrenergic receptor polymorphisms with severe asthma.
BACKGROUND
There is considerable interest in the role of different candidate loci in the development of asthma. This study investigates the association between asthma severity and previously identified polymorphisms at two sites within the beta2-adrenergic receptor (beta2AR) gene: the Arg16-->Gly16 and Gln27-->Glu27 alleles.


METHODS
Restriction enzyme analysis of amplified beta2AR gene products (PCR-RFLP) was used to analyse the frequency of the Arg16-->Gly16 and Gln27-->Glu27 polymorphisms within the beta2AR gene in 95 severe asthmatic patients (with a markedly increased risk of death from asthma), 59 mild asthmatic patients, and a control group of 92 nonasthmatic subjects.


RESULTS
The Gly16 polymorphism was significantly associated with asthma severity with odds ratios (95% CI) for the Gly16 allele being 1.56 (1.02-2.40, P = 0.04) and 0. 98 (0.61-1.57, P = 0.92) for the severe and mild asthma groups, respectively. The corresponding odds ratios (95% CI) for Gly16 homozygotes were 1.91 (0.82-4.41, P = 0.13) and 0.82 (0.35-1.92, P = 0.65) for the severe and mild asthma groups, respectively. There was no significant association between either polymorphism at amino acid 27 and asthma or asthma severity.


CONCLUSIONS
We conclude that the polymorphisms of amino acids 16 and 27 of the beta2AR gene are not associated with the development of asthma per se, but that the Gly16 polymorphism may play a role in the pathogenesis of asthma severity.
Malaghan Institute of Medical Research, Wellington South, New Zealand.
J W
JW
Holloway
P R
PR
Dunbar
G A
GA
Riley
G M
GM
Sawyer
P F
PF
Fitzharris
N
N
Pearce
G S
GS
Le Gros
R
R
Beasley
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D001249:Asthma / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
D018343:Receptors, Adrenergic, beta-2