The glutamine 27 beta2-adrenoceptor polymorphism is associated with elevated IgE levels in asthmatic families.
BACKGROUND
The beta2-adrenoceptor polymorphisms occurring at amino acid positions 16 (arginine to glycine) and 27 (glutamine to glutamate) are known to be functionally relevant and also disease-modifying in subjects with asthma. However, the contribution of these polymorphisms to the development of the asthmatic phenotype or other markers for allergic disease remains to be established.


OBJECTIVE
This large family study examines the contributions of these polymorphisms in determining the heritable component of markers for allergic disease in asthmatic families.


METHODS
Three hundred twenty-four individuals from 60 families multiplex for asthma selected by means of an asthmatic proband were characterized for the following markers of allergic disease: asthma, atopy, and serum IgE. The polymerase chain reaction was used to generate a 234 base pair fragment spanning the region of interest, and the beta2-adrenoceptor polymorphism was then defined by allele-specific oligonucleotide hybridization. Segregation analysis was then performed.


RESULTS
We found a significant association (p = 0.009) between the glutamine 27 beta2-adrenoceptor polymorphism and elevated levels of IgE, which was supported by the observation of linkage between IgE and beta2-adrenoceptor polymorphisms at locus 27 (p = 0.037). However, there was no association between either the arginine-glycine 16 or the glutamine-glutamate 27 beta2-adrenoceptor polymorphism and an increased risk of asthma or atopy per se.


CONCLUSIONS
The glutamine 27 beta2-adrenoceptor polymorphism appears to contribute to IgE variability in families with asthma. However, it seems that although both amino acid 16 and 27 beta2-adrenoceptor polymorphisms are disease-modifying in subjects with asthma, they do not contribute markedly to the development of the asthmatic phenotype.
Dewar
J C
JC
Department of Therapeutics, University Hospital, Nottingham, United Kingdom.
Wilkinson
J
J
Wheatley
A
A
Thomas
N S
NS
Doull
I
I
Morton
N
N
Lio
P
P
Harvey
J F
JF
Liggett
S B
SB
Holgate
S T
ST
Hall
I P
IP
D000328:Adult; D000483:Alleles; D001249:Asthma / Q000097:blood* / Q000235:genetics*; D002648:Child; D005192:Family Health; D005260:Female; D005973:Glutamine / Q000235:genetics*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D008297:Male; D009693:Nucleic Acid Hybridization; D011110:Polymorphism, Genetic / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
D018343:Receptors, Adrenergic, beta-2; D005973:Glutamine; D007073:Immunoglobulin E